Volume 208 - Issue 3
Managing menopausal symptoms after cancer: an evidence-based approach for primary care
Authors: Jennifer L Marino, Helen C McNamara and Martha Hickey
Med J Aust 2018; 208 (3): 127-132. || doi: 10.5694/mja17.00693
Published online: 19 February 2018
Published online: 19 February 2018
Menopausal symptoms are often the most persistent and troubling effects of cancer treatment
Summary
- Impaired ovarian function and menopausal symptoms are common after cancer treatment.
- Menopausal symptoms often occur at an earlier age in women with cancer, and may be more severe than in natural menopause; they may be the most persistent and troubling sequelae of cancer.
- A third of female patients with cancer report dissatisfaction with the quality and length of physician–patient discussions about reproductive health, including menopause.
- Systemic menopausal hormone therapy is the most effective treatment for menopausal symptoms, but it is not suitable for all patients after cancer — where it is unsuitable, alternative effective non-hormonal treatments are available.
- Effective pharmacological agents available to treat vasomotor symptoms include selective serotonin reuptake inhibitors, serotonin–noradrenaline reuptake inhibitors, clonidine and gabapentin. There is increasing evidence supporting cognitive behavioural therapy for the treatment of vasomotor symptoms, in self-help or group settings.
- Vaginal atrophy can be treated with vaginal (topical) oestrogen with minimal systemic absorption; topical vaginal lubricants may help with vaginal dryness and dyspareunia, with some evidence suggesting that silicone-based products may be more effective than water-based ones.
- Bone health may be impaired in post-menopausal women with cancer or in cancer survivors, particularly in women with treatment-related menopause or in women receiving anti-oestrogen therapies; this should be managed in addition to menopausal symptoms.
- Primary care physicians should be aware of the troublesome and ongoing nature of menopausal symptoms after cancer, should discuss them with all patients after cancer treatment, and should consider treatment or referral to a specialist for appropriate management.
Menopause, the final menstrual period, is a normal reproductive stage for women. Natural menopause occurs at an average age of 51 years in women of Western origin.1 Symptoms related to the endocrine changes at this time include vasomotor symptoms (hot flushes and night sweats), vulvovaginal symptoms (vulvovaginal dryness, itching and discomfort) and dyspareunia.2 In addition, sleep disturbance also increases across the menopause transition; this may be secondary to vasomotor symptoms.3 Other common mid-life symptoms include cognitive, mood and musculoskeletal problems; however, it is unclear whether these are due to menopause or ageing.
Around 171 400 Australian women, or 1.5% of the female population, are estimated to live with cancer.4 In females aged under 25 years, leukaemia, lymphoma and melanoma are the most commonly diagnosed cancers, while in those aged 25–49 years, breast cancer, melanoma and thyroid cancer are most common.5 Treatment for these conditions, or consequences of the cancer itself, often leads to early menopause or menopausal symptoms. In a meta-analysis of 45 studies of cancer survivors diagnosed from childhood to 40 years, the median age at menopause was found to be 44 years.6 This may contribute to patient distress. Moreover, for many breast cancer survivors, menopausal symptoms are among the most persistent and bothersome effects of treatment and may be more common and severe than in other women.7,8
While the diagnosis of reproductive stages in women, including menopause, has been standardised,9 diagnosing menopause in cancer survivors can be difficult, as ovulation may resume after 2 or more years of chemotherapy-induced amenorrhoea and raised follicle-stimulating hormone.10 This has potential implications for accessing advice or treatment for menopausal symptoms. Little is known about care-seeking and treatment uptake for menopausal symptoms in cancer survivors, or about satisfaction with treatment options for these symptoms, but a third of women with cancer report dissatisfaction with the quality and length of physician–patient discussions about reproductive health, including menopause, before their cancer treatment.11
This review provides a summary of the evidence with respect to the treatment of menopause in cancer survivors. We searched PubMed for English language articles about cancer and menopause or menopausal symptoms, and reviewed relevant specialty guidelines and leading oncology, cancer supportive care and menopause journals. Where sufficient evidence is available, recommendations regarding treatment options are provided.
Mechanisms of cancer-related menopause
The way in which menopause or menopausal symptoms are induced varies according to cancer type and treatment modality, and may result from surgery, chemotherapy or radiotherapy treatment for cancer, or may be related to the effects of ongoing anti-oestrogen medication (Box). Moreover, women diagnosed with breast cancer will be advised to discontinue treatment with menopausal hormone therapy (MHT), commonly leading to recurrent menopausal symptoms.
Surgical menopause
Bilateral oophorectomy in pre-menopausal women — which, in conjunction with bilateral salpingectomy, may be used as a treatment for endometrial and ovarian cancer or may be recommended as a risk-reduction treatment for pre-menopausal women at high inherited risk of ovarian or breast cancer (eg, women with a BRCA1 or BRCA2 gene mutation) — induces surgical menopause.12 Despite the lack of large prospective studies in cancer survivors, surgical menopause appears to cause more frequent and severe vasomotor and sexual symptoms than natural menopause.12,13 Symptoms associated with surgical menopause as treatment for gynaecological cancer or to reduce the risk of breast cancer recurrence may, however, be difficult to distinguish from those associated with adjuvant treatments.
Radiation-induced menopause
Ovarian function is highly susceptible to ionising radiation.14 Cancers in the abdomen and pelvis are frequently treated with beam radiation or brachytherapy and the ovaries are usually exposed. Pelvic radiation for cervical or colorectal cancer generally leads to ovarian failure.14 In pre-menopausal patients who have pelvic radiotherapy for cancers not involving the ovary, it is possible to surgically move one or both ovaries out of the field of radiation before local irradiation. A recent meta-analysis found that, with this procedure, ovarian function is preserved in around 70% of patients,15 but whether ovarian transposition improves pregnancy outcomes is uncertain.
In addition to ovarian effects, pelvic irradiation causes persistent endometrial and myometrial atrophy and myometrial fibrosis.16 Radiation damage to the vaginal mucosa may result in adhesions, ulceration, atrophy and fibrosis, causing shortening and tightening of the vaginal canal (vaginal stenosis) in about a third of patients, with a range of 1.25–88% depending on the dose and site of radiation and concomitant therapy.17
Chemotherapy-induced menopause
Adjuvant chemotherapy regimens used for common female cancers may be gonadotoxic.18 In a study of childhood and young adult cancer, the chemotherapy regimens most associated with early non-surgical menopause included alkylating agents, possibly related to cyclophosphamide dose.6 The severity of vasomotor symptoms does not appear to differ among patients with cancer by chemotherapy history, although dyspareunia may be worse after chemotherapy.7,19
Endocrine therapy-induced menopausal symptoms
The use of endocrine therapy to minimise oestradiol levels is recommended as adjuvant therapy for women with oestrogen-receptor-positive breast cancer20-22 and as prophylaxis for those who are at high inherited risk of breast cancer.23 The treatment of breast cancer in post-menopausal women commonly includes endocrine therapy for up to 10 years;24 moreover, in pre-menopausal women, ovarian suppression with gonadotrophin-releasing hormone agonists supplemental to endocrine therapy increases the prevalence of hot flushes.25
Endocrine therapy, whether tamoxifen or aromatase inhibitors, causes vasomotor symptoms in up to 80% of women19 — these have been shown to be more severe among women prescribed tamoxifen.26 Moreover, tamoxifen and aromatase inhibitors are both associated with sexual dysfunction, including vaginal dryness, dyspareunia and loss of sexual interest,19,27 which may persist for years after exposure7 and are more severe with aromatase inhibitors.19,28 Up to 50% of women fail to complete 5 years of endocrine therapy;29 switching agents to manage side effects is common and may be effective in up to 58–77% of patients.30,31 A recent substudy in a randomised controlled trial of letrozole and exemestane found that in women who discontinued their assigned medication due to intolerance (n = 83), switching medication improved patient outcomes, including vasomotor, but not vulvovaginal, symptoms without significant change in oestradiol levels.32
Haemopoietic stem cell transplantation
Primary ovarian failure occurs after high dose chemotherapy and radiotherapy required for stem cell transplantation.33 In many haematological malignancies, conditioning therapy before stem cell transplantation includes total body irradiation; however, it is difficult to differentiate the influence of total body irradiation on ovarian function from that of concomitant gonadotoxic chemotherapy.33 Moreover, in up to 50% of patients undergoing haematopoietic stem cell transplant, genital graft-versus-host disease may occur.33 Signs of female genital graft-versus-host disease include vulvar erythema and erosions and vulvovaginal scarring, and the symptoms of vulvovaginal dryness, itching and pain and dyspareunia are similar to those of menopausal genital atrophy. This disease may also result in vaginal stenosis and its diagnosis may be difficult without biopsy.33
Management options
Menopausal hormone therapy
Treatment of cancer-related menopause depends on the type of cancer and the source of menopausal symptoms. MHT is the preferred therapy for patients experiencing cancer-related menopause close to the natural age of menopause and when cancer does not complicate the decision to prescribe it. Organisations such as the Royal Australian and New Zealand College of Obstetricians and Gynaecologists,34 the United Kingdom National Institute for Health and Care Excellence,35 the North American Menopause Society36 and the European Menopause and Andropause Society37 all provide recommendations for managing menopausal symptoms. MHT, also known as hormone replacement therapy or hormone therapy, consists of oestrogen supplementation with or without a progestogen. It may be administered systemically, as oral or transdermal therapy, or topically to manage vaginal symptoms. Systemic MHT is the most effective treatment for vasomotor symptoms and may improve sleep in women who experience these symptoms at night.38 For women with an intact uterus, a progestogen should be added to prevent endometrial hyperplasia or endometrial cancer.39 Tibolone, a selective oestrogen receptor modulator with anti-oestrogenic activity in the endometrium, may also be used to treat vasomotor symptoms, but it appears to be less effective than oestrogen-based MHT.40
The principal safety concern with the use of MHT in cancer survivors is whether it is likely to cause disease progression or recurrence. The evidence base varies by cancer type, and considerations include whether the particular cancer is oestrogen-sensitive and whether there is human clinical evidence that oestrogen therapy stimulates tumour growth or recurrence after definitive treatment.
Menopausal hormone therapy after breast cancer
While there is little evidence regarding the risks of systemic MHT after breast cancer,41 international consensus, including guidance from the Royal Australian and New Zealand College of Obstetricians and Gynaecologists,42 advises against its use after any breast cancer.21,43 Moreover, tibolone increases the risk of breast cancer recurrence44 and should not be prescribed.
Menopausal hormone therapy after haematological cancers
There is limited evidence suggesting that MHT use is safe after haematological cancers, including leukaemia, lymphoma and multiple myeloma.45 MHT is recommended until the age of natural menopause in all women experiencing premature ovarian insufficiency,35 which includes over 90% of pre-menopausal women treated with haematopoietic stem cell transplant.35,45 Transdermal preparations of MHT may be preferable, as women with a history of haematological cancer may already be at increased risk of thromboembolic events related to their disease.35,46
Menopausal hormone therapy after colorectal cancer
While it has been thought that MHT may be safely used for symptomatic women after colorectal cancer, specific safety data are limited and mixed. Observational data suggest that MHT after colorectal cancer is associated with lower disease-specific mortality.45,47 Evidence is also extrapolated from analyses of the data from the Women’s Health Initiative randomised controlled trials. Initial analyses suggested that combined MHT reduced the incidence of colorectal cancer, but more recently, cumulative 18-year follow-up data from these trials have shown that, in the pooled cohort, colorectal cancer mortality was not significantly different in either trial. However, in an age-stratified analysis of the data, there was an increased rate of colorectal cancer mortality in women aged 70–79 years in the oestrogen-alone trial.48
Menopausal hormone therapy after lung cancer
MHT does not appear to affect lung cancer incidence,47 but oestrogen receptors are expressed in normal and malignant lung tissue. In post hoc analyses of the Women’s Health Initiative data, combined MHT was associated with increased risk of mortality from lung cancer independent of smoking status, and it is therefore recommended that women at high risk for lung cancer be informed of this risk.47 There are currently no specific data or guidelines about MHT use after lung cancer.
Menopausal hormone therapy after gynaecological cancers
In women with non-oestrogen-dependent gynaecological malignancies, including vulvar and vaginal cancer, squamous cell carcinoma of the cervix and most uterine cancers, MHT can be used in the short term to manage vasomotor and vaginal symptoms.49 Although most endometrial cancers are considered oestrogen-dependent, there is limited evidence that oestrogen can be used safely for women with low-grade, early-stage endometrial cancer;49,50 there are no data on oestrogen use after advanced endometrial cancer. Moreover, new guidelines from the North American Menopause Society consider prior oestrogen-dependent endometrial cancer a contraindication to MHT use.36 Limited observational data show no adverse outcomes of MHT in survivors of epithelial ovarian carcinoma, but oestrogen receptors are frequently expressed in low-grade serous carcinoma, so this therapy cannot be recommended in serous subtypes.49,50 Safety data do not exist for other potentially oestrogen-dependent tumours, which include uterine sarcoma, cervical adenocarcinoma, granulosa cell tumours and other sex cord-stromal tumours, and, therefore, MHT should be avoided.50
Menopausal hormone therapy after melanoma
Malignant melanoma has long been considered an oestrogen-dependent cancer, but observational data are mixed around the role of MHT in disease progression and prognosis.45 Further evidence is required to establish the safety of MHT after melanoma.
Bioidentical hormone therapy
Custom-compounded or bioidentical ovarian hormones appear superior to placebo in relieving moderate-to-severe hot flushes; however, their effectiveness relative to conventional MHT, the long term safety and the safety in patients with cancer have not been established.51 Moreover, these drugs are not regulated by the Australian Therapeutic Goods Administration and their use cannot be recommended, particularly among cancer survivors.
Vaginal oestrogens
Local (vaginal) oestrogens have been shown to be effective in dealing with vulvovaginal atrophy.35,52,53 A recent systematic review found no evidence that adverse events (a proxy for systemic absorption) differed between vaginal oestrogen and placebo.52 Moreover, a recent study of the vaginal ring in post-menopausal patients with early breast cancer who were taking aromatase inhibitors found that these oestrogens improved vaginal atrophy and sexual quality of life without a persistent increase in systemic oestradiol.54 However, the use of vaginal oestrogens in patients with breast cancer remains controversial and an individualised, case-dependent approach should be maintained. In all cases, it is recommended to establish a close liaison with the patient’s treating surgical and oncological teams.
Non-hormonal therapies
Vasomotor symptoms of menopause
Vasomotor symptoms may be treated effectively with selective serotonin reuptake inhibitors (citalopram, escitalopram, sertraline, fluoxetine, paroxetine), serotonin–noradrenaline reuptake inhibitors (venlafaxine, desvenlafaxine), clonidine and gabapentin.2,55 Citalopram (10–20 mg daily) has been specifically examined in patients with breast cancer and has been shown to reduce the frequency of hot flushes, with study participants being followed up to a maximum of 7 weeks.56 Data examining sertraline use in patients with breast cancer are limited and therefore it should not be recommended.57 Fluoxetine and paroxetine should be avoided in patients using tamoxifen, as they may impair conversion of tamoxifen to its active metabolite.58 Venlafaxine (75 mg extended release daily) reduces the frequency of hot flushes in patients with breast cancer by 10–40%, requires fewer weeks to improve symptoms than clonidine, and patients prefer it to gabapentin.59
Cognitive behavioural therapy, in group or self-help settings, reduces the impact, but not the frequency, of vasomotor symptoms in patients with breast cancer.60 In addition, the use of clinical hypnosis appears promising, with a study of 51 breast cancer survivors showing improvements in vasomotor symptoms, mood and sleep.61 Supplementary phytoestrogens may reduce vasomotor symptoms and vaginal dryness, but the evidence is of low to moderate quality.62 Moreover, the evidence available does not support the use of black cohosh,62 acupuncture,63 relaxation techniques,64 yoga55 or exercise65 to manage vasomotor symptoms, and the stellate ganglion block — an injection of a local anaesthetic into sympathetic nerve fibres to disrupt temperature regulation — is invasive, costly and there is insufficient evidence for efficacy in treating vasomotor symptoms.55
Vaginal symptoms of menopause
Vaginal dryness may be treated with vaginal moisturisers and lubricants. The North American Menopause Society recommends the use of vaginal moisturisers to relieve symptoms of vaginal dryness,53 but there is little evidence to support their effectiveness.66 Vaginal lubricants are substances applied to contact surfaces to reduce friction during sexual activity, and common lubricant bases include water, mineral oils, plant oils and polymerised siloxanes (ie, silicone-based lubricants). Oil-based lubricants cannot be used with latex condoms, and both oil- and silicone-based products persist longer than water-based products and may require washing with soap and water for removal.67 Glycols (eg, glycerine and propylene glycol) may be added to water-based lubricants to increase persistence, but they increase osmolality and the risk of epithelial disruption.68 A randomised controlled trial of water- and silicone-based lubricants found that the silicone-based lubricant was more effective at reducing pain during sexual activity in patients with breast cancer.69 Additionally, an intervention combining olive oil (as a lubricant), vaginal moisturiser and pelvic floor muscle relaxation significantly improved dyspareunia, sexual function and quality of life and may therefore be recommended.70
Menopause-specific sleep disturbance
Menopause-specific sleep disturbance has received limited attention in trials of non-hormonal therapies for menopausal symptoms in patients with cancer. In trials measuring vasomotor symptoms in healthy women, escitalopram, paroxetine, venlafaxine, desvenlafaxine and gabapentin have been shown to improve vasomotor functions and sleep.2 However, adverse side effects of selective serotonin reuptake inhibitors and serotonin–noradrenaline reuptake inhibitors include somnolence and insomnia. In breast cancer survivors who have hot flushes, augmentation of treatment with zolpidem (10 mg nightly) improves sleep and quality of life,71 and level one data show that cognitive behavioural therapy can also improve sleep in cancer survivors.72
Bone density
During the menopausal transition, bone mineral density decreases and fracture risk increases,73,74 and in patients with cancer, early menopause, aromatase inhibitors, radiation and corticosteroids can further increase fracture risk.75 Systemic MHT has been shown to reduce osteoporotic fracture risk in the general population of post-menopausal women,47 and it is recommended for bone health in all women experiencing menopause before the age of 40 years, including cancer-related menopause, until the age of natural menopause, except when contraindicated.35 Moreover, the European Society for Medical Oncology recommends assessment of clinical risk factors and measurement of bone density by dual energy x-ray absorptiometry scan at baseline and at intervals of 1–2 years for all patients at risk for bone loss due to endocrine therapy or oophorectomy.75 Regular exercise, calcium intake of 1000 mg daily and vitamin D supplementation of 1000–2000 units daily are also recommended.75 In women whose bone mineral density T score at the spine or hip is less than -2.0, antiresorptive therapy with bisphosphonates or denosumab should be initiated.75 In addition, bisphosphonates extend survival and reduce the recurrence and frequency of metastasis in post-menopausal women with breast cancer.76
Conclusions
For many women who live with or survive cancer, menopausal symptoms are persistent and troubling effects of cancer treatment. Systemic MHT provides symptom control and may be used after low-grade, early-stage endometrial cancer, squamous cell cervical cancer and vulvar and vaginal cancers, but it should be avoided after breast cancer and after other oestrogen-dependent gynaecological malignancies. There is mixed evidence regarding MHT use after colorectal cancer and localised malignant melanoma, and its safety after lung cancer is unknown. Effective non-hormonal methods to manage vasomotor symptoms include cognitive behavioural therapy, selective serotonin reuptake inhibitor, serotonin–noradrenaline reuptake inhibitor, clonidine and gabapentin. Vaginal oestrogen may be useful to address vaginal dryness and has not been shown to cause a persistent increase in systemic oestradiol, and lubricants may also help with dyspareunia. Post-menopausal women with cancer and cancer survivors, particularly those with treatment-related menopause or who are using anti-oestrogen therapies, may have impaired bone health, which should be managed in addition to menopausal symptoms. Primary care physicians should be aware of the troublesome and ongoing nature of menopausal symptoms after cancer, should discuss them with all patients after cancer treatment, and should consider treatment or referral to a specialist for appropriate management.
Box – Mechanisms leading to menopause or menopausal symptoms in cancer patients
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Cause of menopause |
Indication for treatment |
Proposed mechanism of menopause |
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Chemotherapy (especially cyclophosphamide, procarbazine, and other alkylating agents) |
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Bilateral salpingo-oophorectomy |
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Anti-oestrogen endocrine therapy |
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Radiation |
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Competing interests
No relevant disclosures.
Acknowledgements
M Hickey is supported by a National Health and Medical Research Council Practitioner Fellowship.
References
- Mishra GD, Kuh D. Health symptoms during midlife in relation to menopausal transition: British prospective cohort study. BMJ 2012; 344: e402.
- Hickey M, Szabo RA, Hunter MS. Non-hormonal treatments for menopausal symptoms. BMJ 2017; 359: j5101.
- Pinkerton JV, Abraham L, Bushmakin AG, et al. Relationship between changes in vasomotor symptoms and changes in menopause-specific quality of life and sleep parameters. Menopause 2016; 23: 1060-1066.
- Australian Bureau of Statistics. National Health Survey: first results, 2014–15 (ABS Cat. No. 4364.0.55.001). Canberra: Commonwealth of Australia; 2015. http://www.ausstats.abs.gov.au/ausstats/subscriber.nsf/0/CDA852A349B4CEE6CA257F150009FC53/$File/national%20health%20survey%20first%20results,%202014-15.pdf (viewed Dec 2017).
- Australian Institute of Health and Welfare. Cancer in Australia 2017 (AIHW Cat. No. CAN 100; Cancer Series No. 101). Canberra: AIHW; 2017. https://www.aihw.gov.au/getmedia/3da1f3c2-30f0-4475-8aed-1f19f8e16d48/20066-cancer-2017.pdf.aspx?inline=true (viewed Dec 2017).
- Overbeek A, van den Berg MH, van Leeuwen FE, et al. Chemotherapy-related late adverse effects on ovarian function in female survivors of childhood and young adult cancer: a systematic review. Cancer Treat Rev 2017; 53: 10-24.
- Davis SR, Panjari M, Robinson PJ, et al. Menopausal symptoms in breast cancer survivors nearly 6 years after diagnosis. Menopause 2014; 21: 1075-1081.
- Marino JL, Saunders CM, Emery LI, et al. Nature and severity of menopausal symptoms and their impact on quality of life and sexual function in cancer survivors compared with women without a cancer history. Menopause 2014; 21: 267-274.
- Harlow SD, Gass M, Hall JE, et al. Executive summary of the Stages of Reproductive Aging Workshop + 10: addressing the unfinished agenda of staging reproductive aging. Menopause 2012; 19: 387-395.
- Sukumvanich P, Case LD, Van Zee K, et al. Incidence and time course of bleeding after long-term amenorrhea after breast cancer treatment: a prospective study. Cancer 2010; 116: 3102-3111.
- Scanlon M, Blaes A, Geller M, et al. Patient satisfaction with physician discussions of treatment impact on fertility, menopause and sexual health among pre-menopausal women with cancer. J Cancer 2012; 3: 217-225.
- Vermeulen RFM, Beurden MV, Korse CM, et al. Impact of risk-reducing salpingo-oophorectomy in premenopausal women. Climacteric 2017; 20: 212-221.
- Blumel JE, Chedraui P, Baron G, et al. A large multinational study of vasomotor symptom prevalence, duration, and impact on quality of life in middle-aged women. Menopause 2011; 18: 778-785.
- Irtan S, Orbach D, Helfre S, et al. Ovarian transposition in prepubescent and adolescent girls with cancer. Lancet Oncol 2013; 14: E601-E608.
- Mossa B, Schimberni M, Di Benedetto L, Mossa S. Ovarian transposition in young women and fertility sparing. Eur Rev Med Pharmacol Sci 2015; 19: 3418-3425.
- Teh WT, Stern C, Chander S, Hickey M. The impact of uterine radiation on subsequent fertility and pregnancy outcomes. Biomed Res Int 2014; 2014: 482968.
- Morris L, Do V, Chard J, Brand AH. Radiation-induced vaginal stenosis: current perspectives. Int J Womens Health 2017; 9: 273-279.
- Peate M, Stafford L, Hickey M. Fertility after breast cancer and strategies to help women achieve pregnancy. Cancer Forum 2017; 41: 32-39.
- Marino JL, Saunders CM, Emery LI, et al. How does adjuvant chemotherapy affect menopausal symptoms, sexual function, and quality of life after breast cancer? Menopause 2016; 23: 1000-1008.
- National Institute for Health and Care Excellence. Advanced breast cancer: diagnosis and treatment [website]. Clinical guideline CG81. London: NICE; 2009. https://www.nice.org.uk/guidance/cg81 (viewed Dec 2017).
- National Institute for Health and Care Excellence. Early and locally advanced breast cancer: diagnosis and treatment. Clinical guideline CG80. London: NICE; 2009. https://www.nice.org.uk/guidance/cg80 (viewed Dec 2017).
- Cancer Australia. Recommendations for aromatase inhibitors as adjuvant endocrine therapy for post-menopausal women with hormone receptor-positive early breast cancer. Sydney: Cancer Australia; 2006. https://guidelines.canceraustralia.gov.au/guidelines/adjuvant_endocrine_therapy/ch01.php (viewed Dec 2017).
- National Institute for Health and Care Excellence. Familial breast cancer: classification, care and managing breast cancer and related risks in people with a family history of breast cancer. Clinical guideline CG164. London: NICE; 2017. https://www.nice.org.uk/guidance/cg164 (viewed Dec 2017).
- Burstein HJ, Temin S, Anderson H, et al. Adjuvant endocrine therapy for women with hormone receptor–positive breast cancer: American Society of Clinical Oncology clinical practice guideline focused update. J Clin Oncol 2014; 32: 2255-2269.
- Francis PA, Regan MM, Fleming GF, et al. Adjuvant ovarian suppression in premenopausal breast cancer. N Engl J Med 2015; 372: 436-446.
- Forbes JF, Sestak I, Howell A, et al. Anastrozole versus tamoxifen for the prevention of locoregional and contralateral breast cancer in postmenopausal women with locally excised ductal carcinoma in situ (IBIS-II DCIS): a double-blind, randomised controlled trial. Lancet 2016; 387: 866-873.
- Chin SN, Trinkaus M, Simmons C, et al. Prevalence and severity of urogenital symptoms in postmenopausal women receiving endocrine therapy for breast cancer. Clin Breast Cancer 2009; 9: 108-117.
- Baumgart J, Nilsson K, Evers AS, et al. Sexual dysfunction in women on adjuvant endocrine therapy after breast cancer. Menopause 2013; 20: 162-168.
- Hershman DL, Kushi LH, Shao T, et al. Early discontinuation and nonadherence to adjuvant hormonal therapy in a cohort of 8,769 early-stage breast cancer patients. J Clin Oncol 2010; 28: 4120-4128.
- Güth U, Myrick ME, Schötzau A, et al. Drug switch because of treatment-related adverse side effects in endocrine adjuvant breast cancer therapy: how often and how often does it work? Breast Cancer Res Treat 2011; 129: 799-807.
- Kwan ML, Roh JM, Laurent CA, et al. Patterns and reasons for switching classes of hormonal therapy among women with early-stage breast cancer. Cancer Causes Control 2017; 28: 557-562.
- Kadakia KC, Kidwell KM, Seewald NJ, et al. Prospective assessment of patient-reported outcomes and estradiol and drug concentrations in patients experiencing toxicity from adjuvant aromatase inhibitors. Breast Cancer Res Treat 2017; 164: 411-419.
- Brennan A, Hickey M. Gynaecological care after stem cell transplant: an overview. Maturitas 2017; 105: 30-32.
- Royal Australian and New Zealand College of Obstetricians and Gynaecologists. Menopausal hormone therapy advice (C-GYN 16). Melbourne: RANZCOG; 2015. https://www.ranzcog.edu.au/RANZCOG_SITE/media/RANZCOG-MEDIA/Women%27s%20Health/Statement%20and%20guidelines/Clinical%20-%20Gynaecology/Menopausal-Hormone-Therapy-Advice-(C-Gyn-16)-Re-write-July-2015.pdf?ext=.pdf (viewed Dec 2017).
- National Institute for Health and Care Excellence. Menopause: diagnosis and management. NICE guideline NG23. London: NICE; 2015. https://www.nice.org.uk/guidance/ng23 (viewed Dec 2017).
- Pinkerton JV, Aguirre FS, Blake J, et al. The 2017 hormone therapy position statement of the North American Menopause Society. Menopause 2017; 24: 728-753.
- Armeni E, Lambrinoudaki I, Ceausu I, et al. Maintaining postreproductive health: a care pathway from the European Menopause and Andropause Society (EMAS). Maturitas 2016; 89: 63-72.
- Cintron D, Lipford M, Larrea-Mantilla L, et al. Efficacy of menopausal hormone therapy on sleep quality: systematic review and meta-analysis. Endocrine 2017; 55: 702-711.
- Furness S, Roberts H, Marjoribanks J, et al. Hormone therapy in postmenopausal women and risk of endometrial hyperplasia. Cochrane Database Syst Rev 2012; (8): CD000402.
- Formoso G, Perrone E, Maltoni S, et al. Short-term and long-term effects of tibolone in postmenopausal women. Cochrane Database Syst Rev 2016; (10): CD008536.
- Fahlen M, Fornander T, Johansson H, et al. Hormone replacement therapy after breast cancer: 10 year follow up of the Stockholm randomised trial. Eur J Cancer 2013; 49: 52-59.
- Royal Australian and New Zealand College of Obstetricians and Gynaecologists. Management of the menopause after breast cancer (CGYN-15). Melbourne: RANZCOG; 2014. https://www.ranzcog.edu.au/RANZCOG_SITE/media/RANZCOG-MEDIA/Women's%20Health/Statement%20and%20guidelines/Clinical%20-%20Gynaecology/Management-of-the-Menopause-after-Breast-Cancer-(C-Gyn-15)-Review-November-2014.pdf?ext=.pdf (viewed Dec 2017).
- de Villiers TJ, Hall JE, Pinkerton JV, et al. Revised global consensus statement on menopausal hormone therapy. Climacteric 2016; 19: 313-315.
- Kenemans P, Bundred NJ, Foidart JM, et al. Safety and efficacy of tibolone in breast-cancer patients with vasomotor symptoms: a double-blind, randomised, non-inferiority trial. Lancet Oncol 2009; 10: 135-146.
- Kuhle CL, Kapoor E, Sood R, et al. Menopausal hormone therapy in cancer survivors: a narrative review of the literature. Maturitas 2016; 92: 86-96.
- Falanga A, Marchetti M. Venous thromboembolism in the hematologic malignancies. J Clin Oncol 2009; 27: 4848-4857.
- Marjoribanks J, Farquhar C, Roberts H, et al. Long-term hormone therapy for perimenopausal and postmenopausal women. Cochrane Database Syst Rev 2017; (1): CD004143.
- Manson JE, Aragaki AK, Rossouw JE, et al. Menopausal hormone therapy and long-term all-cause and cause-specific mortality: the Women’s Health Initiative randomized trials. JAMA 2017; 318: 927-938.
- Del Carmen MG, Rice LW. Management of menopausal symptoms in women with gynecologic cancers. Gynecol Oncol 2017; 146: 427-435.
- O’Donnell RL, Clement KM, Edmondson RJ. Hormone replacement therapy after treatment for a gynaecological malignancy. Curr Opin Obstet Gynecol 2016; 28: 32-41.
- Gaudard AM, Silva de Souza S, Puga ME, et al. Bioidentical hormones for women with vasomotor symptoms. Cochrane Database Syst Rev 2016; (8): CD010407.
- Lethaby A, Ayeleke RO, Roberts H. Local oestrogen for vaginal atrophy in postmenopausal women. Cochrane Database Syst Rev 2016; (8): CD001500.
- Shifren JL, Gass MLS, Care NRC. The North American Menopause Society recommendations for clinical care of midlife women. Menopause 2014; 21: 1038-1062.
- Melisko ME, Goldman ME, Hwang J, et al. Vaginal testosterone cream vs estradiol vaginal ring for vaginal dryness or decreased libido in women receiving aromatase inhibitors for early-stage breast cancer: A randomized clinical trial. JAMA Oncol 2017; 3: 313-319.
- Carpenter J, Gass MLS, Maki PM, et al. Nonhormonal management of menopause-associated vasomotor symptoms: 2015 position statement of The North American Menopause Society. Menopause 2015; 22: 1155-1174.
- Barton DL, LaVasseur BI, Sloan JA, et al. Phase III, placebo-controlled trial of three doses of citalopram for the treatment of hot flashes: NCCTG trial N05C9. J Clin Oncol 2010; 28: 3278-3283.
- Rada G, Capurro D, Pantoja T, et al. Non-hormonal interventions for hot flushes in women with a history of breast cancer. Cochrane Database Syst Rev 2010; (9): CD004923.
- Drewe J, Bucher KA, Zahner C. A systematic review of non-hormonal treatments of vasomotor symptoms in climacteric and cancer patients. Springerplus 2015; 4: 65.
- Johns C, Seav SM, Dominick SA, et al. Informing hot flash treatment decisions for breast cancer survivors: a systematic review of randomized trials comparing active interventions. Breast Cancer Res Treat 2016; 156: 415-426.
- Hunter MS, Griffiths A, Mann E, et al. NICE guidance on menopause: cognitive behavioural therapy is an effective non-hormonal intervention for managing vasomotor symptoms. BMJ 2015; 351.
- Elkins G, Marcus J, Stearns V, et al. Randomized trial of a hypnosis intervention for treatment of hot flashes among breast cancer survivors. J Clin Oncol 2008; 26: 5022-5026.
- Franco OH, Chowdhury R, Troup J, et al. Effects of natural and plant-based therapies on menopausal symptoms: a systematic review and meta-analysis. Menopause 2016; 23: 1397-1397.
- Dodin S, Blanchet C, Marc I, et al. Acupuncture for menopausal hot flushes. Cochrane Database Syst Rev 2013; (7): CD007410.
- Saensak S, Vutyavanich T, Somboonporn W, et al. Relaxation for perimenopausal and postmenopausal symptoms. Cochrane Database Syst Rev 2014; (7): CD008582.
- Daley A, Stokes-Lampard H, Thomas A, et al. Exercise for vasomotor menopausal symptoms. Cochrane Database Syst Rev 2014; (11): CD006108.
- Loprinzi CL, Abu-Ghazaleh S, Sloan JA, et al. Phase III randomized double-blind study to evaluate the efficacy of a polycarbophil-based vaginal moisturizer in women with breast cancer. J Clin Oncol 1997; 15: 969-973.
- Andelloux M. Products for sexual lubrication: understanding and addressing options with your patients. Nurs Womens Health 2011; 15: 253-257.
- Edwards D, Panay N. Treating vulvovaginal atrophy/genitourinary syndrome of menopause: how important is vaginal lubricant and moisturizer composition? Climacteric 2016; 19: 151-161.
- Hickey M, Allardice K, Wolke L, et al. Silicone vs. water-based lubricant for symptomatic vaginal dryness after breast cancer: Preliminary findings from a randomized trial. Reprod Sci 2015; 22: 63a.
- Juraskova I, Jarvis S, Mok K, et al. The acceptability, feasibility, and efficacy (Phase I/II Study) of the OVERcome (Olive Oil, Vaginal Exercise, and MoisturizeR) intervention to improve dyspareunia and alleviate sexual problems in women with breast cancer. J Sex Med 2013; 10: 2549-2558.
- Joffe H, Partridge A, Giobbie-Hurder A, et al. Augmentation of venlafaxine and selective serotonin reuptake inhibitors with zolpidem improves sleep and quality of life in breast cancer patients with hot flashes: a randomized, double-blind, placebo-controlled trial. Menopause 2010; 17: 908-916.
- Howell D, Oliver TK, Keller-Olaman S, et al. Sleep disturbance in adults with cancer: a systematic review of evidence for best practices in assessment and management for clinical practice. Ann Oncol 2014; 25: 791-800.
- Greendale GA, Sowers M, Han WJ, et al. Bone mineral density loss in relation to the final menstrual period in a multiethnic cohort: Results from the Study of Women’s Health Across the Nation (SWAN). J Bone Miner Res 2012; 27: 111-118.
- Banks E, Reeves GK, Beral V, et al. Hip fracture incidence in relation to age, menopausal status, and age at menopause: Prospective analysis. PLoS Med 2009; 6: e1000181.
- Coleman R, Body JJ, Aapro M, et al. Bone health in cancer patients: ESMO Clinical Practice Guidelines. Ann Oncol 2014; 25: 124-137.
- Coleman R, Powles T, Paterson A, et al. Adjuvant bisphosphonate treatment in early breast cancer: meta-analyses of individual patient data from randomised trials. Lancet 2015; 386: 1353-1361.
Provenance: Commissioned; externally peer reviewed.