Managing Menopausal Symptoms After Breast Cancer: Key Considerations
Menopausal symptoms can significantly impact the quality of life for breast cancer survivors, affecting their tolerance of treatments and overall well-being. Understanding the causes and management strategies for these symptoms is crucial to support these individuals through their post-cancer journey. This article explores the common menopausal symptoms experienced by breast cancer patients, why they occur, the challenges they pose, the duration of hot flushes, and effective management approaches. By addressing these issues, healthcare providers and patients can work together to navigate this aspect of survivorship more effectively.
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Managing Menopausal Symptoms after Breast Cancer Rod Baber
What are menopausal symptoms ? Vasomotor symptoms: hot flushes night sweats Vulvo-vaginal dryness Sleep disturbance Mood disturbance Sexual dysfunction NIH State-of-the-Science Panel. Ann Intern Med 2005
Why do breast cancer patients get menopausal symptoms? Around 60% affected Young women with chemotherapy-induced ovarian failure Young women undergoing oophorectomy Peri and postmenopausal women who stop HRT on diagnosis of breast cancer Pre and postmenopausal women taking endocrine therapy (for up to 10 years) Hot flushes are more frequent and severe than in spontaneous menopause Anti-estrogen therapies may exacerbate symptoms: Vaginal dryness particularly severe with aromatase inhibitors Hickey et al 2008, Kemp et al 2014, Marino et al 2014, Howell et al 2005, ACOG 2014
Why are menopausal symptoms after breast cancer problematic? They may impair quality of life: Worse than the cancer treatment for some women May impact on tolerance of endocrine therapy Up to 40% discontinue because of hot flushes May add to common post-cancer problems such as sleep disturbance and fatigue May have implications for prognosis Risks of early menopause may contribute to morbidity and mortality Osteoporosis and cardiovascular disease Howard-Anderson et al 2012, Chen et al 2013
How long do hot flushes last ? Most around the LMP severe symptoms Mean vasomotor symptoms at natural menopause is 8-10 years duration of Duration after surgical or chemo-induced menopause unknown Politi et al 2008, Col et al 2008, Freeman et al 2014
How can symptoms be managed? Most women have several symptoms Vasomotor symptom are the most common reason to seek treatment, but additive effect of symptoms is unknown Estrogen is the most effective treatment for VMS (85% reduction) and also improves Vulvo-vaginal dryness Potentially mood and sleep Bone health MacLennan et al 2006, Suckling et al 2006, Soares and Frey 2010, Formoso et al 2012
Menopausal symptoms after breast cancer: what can be done? No single non-hormonal treatment for VMS, vaginal symptoms, mood and bone health Need to prioritise and consider multiple interventions Effective non-pharmacological and non-hormonal therapies are available Tailor interventions to individual symptom burden
Managing Menopausal Symptoms after Breast Cancer 1. Assess Cause of menopausal symptoms Treatment induced Discontinued Endocrine menopause HRT Therapy 2. Assess menopausal symptoms Hot flushes, night sweats, insomnia Joint aches and pains, vaginal dryness . 3. Establish what is wanted from Intervention Reduction in (what) symptoms Information / Other outcomes
Managing atrophic vaginitis after breast cancer Prevalence after breast cancer unknown Affects ~ 40% at menopause Vaginal dryness, discomfort, pruritis, dyspareunia, UTI, urgency Worse with AI than tamoxifen Vaginal Lubricants: Sylk, Astroglide, Passion, Wet, Olive oil Vaginal Moisturisers: Replens Vulval Lignocaine gel 4% Vaginal Estrogens -Ovestin (Oestriol), Vagifem (E2) tablets Ospemifene Suckling et al 2006, Dorr et al 2010, Maarmari 2013, Barentsen et al 1997, Burich et al 2012
Managing atrophic vaginitis after breast cancer Vaginal estrogens are the most effective treatment, but are systemically absorbed Vaginal estradiol significantly increases systemic E2 in users of aromatase inhibitors Many oncologists now caution against their use Clinical implications unknown Tamoxifen is probably estrogenic in vagina Kendall et al 2006, Ferrazzi et al 1977, Freidrich et al 1998
Managing atrophic vaginitis after breast cancer Clinical message Avoid vaginal estrogens in AI users If considering then discuss with oncologist Consider vaginal estrogens in TAM users Still discuss with oncologist Relative efficacy of vaginal lubricants unknown Vulval lignocaine (4%) reduces dyspareunia and sexual distress in breast cancer survivors Goetsch et al 2014
Treating VMS without hormones Target day or night VMS Getting a good nights sleep may make the day manageable Review the likely cause of the VMS Early menopause Stopping HRT Endocrine therapy Interventions may differ depending on cause Some VMS improve by swapping endocrine therapies Thomas et al 2008. Hickey et al 2008, Baum et al 2008
Alternative Therapies Phytoestrogens: Pure isoflavones may be effective, but mixed evidence to suggest that supplements are effective. Genistein reduces hot flush frequency (20%) and severity (26%) compared to placebo Black Cohosh: Data mixed but insufficient to recommend Dong Quai: Thought to enhance endogenous estrogens. 1RCT, no better than placebo TCM: Unconvincing data in Western trials, more success in trials of Asian women Acupuncture: Evidence inconclusive Baber R. Maturitas 2010; 66: 344-49 Hickey M, Baber R Drug Safety 2005;28: 1085-1100
Prescription treatments for vasomotor symptoms Clonidine 25-50ug bd Alpha adrenoreceptor agonist, reduces vasoconstriction Clinical effect modest side effects: constipation, dry mouth, drowsiness Long term data lacking Boekhout A H et al. JCO 2011
Gabapentin for hot flushes Gamma amino butyric acid analogue used as anticonvulsant Probably acts as hypothalamic thermoregulatory 4 RCTs show significant reduction in vasomotor symptoms at 900mg per day with a clear dose response relationship Initial side effects include drowsiness, confusion and ataxia Start with 300mg and build up slowly as required Can be used in women already taking SSRI/SNRI Hickey M, Baber R Drug Safety 2005;28: 1085-1100 Butt et al 2008 Reddy et al 2006, Aguirre et al 2010, Pinkerton et al 2014
Pregabalin for hot flashes Loprinzi et al JCO 2010
Antidepressants for hot flushes Name Reduction in hot flushes Duration of studies Additional benefits Improved sleep Nausea, dysfunction Desvenlafaxine 100mg 64% (vs 51% placebo) One year constipation, sexual Improved sleep Nausea, dysfunction Venlafaxine 75mg SR 60% (vs 27% placebo) 8 weeks constipation, sexual Improved sleep, mood, quality of life and hot flash interference Does not impair sexual function. No discontinuation syndr at 10mg Escitalopram (10- 20mg) 55 % (vs 36% placebo) 8 weeks Does not impair sexual function. No discontinuation syndrome Ineffective Citalopram 10mg 49% (vs 23% placebo) 6 weeks 9 months Nausea, dysfunction Ineffective/ AND PAROXETINE? constipation, sexual Fluoxetine 20mg 50% (vs 36% placebo) 6 weeks 9 months Nausea, insomnia. No discontinuation syndrome at lower doses No change in sexual function Improved sleep and reduced burden of hot flashes fatigue, dizzyness, Paroxetine 12.5mg 56% (vs 28% placebo) 6 weeks Paroxetine 7.5mg 43% (vs 37% placebo) 12 weeks 40% (vs 32% placebo) 24 weeks Loprinzi et al 2000 and 2002,Stearns et al 2005, Evans et al 2006, Speroff et al 2008, Pinkerton et Al 2013. Simon et al 2013, Freeman et al 2012, Carpenter et al 2012, Ensrud et al 2012, Joffe et al, in prep, Carpenter et al, 2012, La Croix et al 2012, Reed et al 2012, Suvanto-Luukkonen et al 2005, Pinkerton et al NAMS
Venlafaxine 75mg equivalent to 0.25mg estradiol for VMS Joffe H et al JAMA Internal Medicine July 2014 Volume 174, Number 7
Considerations for SSRI/SRNI Many middle aged women will already be taking SSRI/SNRI for depression Side effects are common Some products discontinuation syndromes Primarily short-acting Paroxetine, (des)venlafaxine Fluoxetine and paroxetine may interact with tamoxifen may cause agents: Stearns et al 2004, 2006, Jin et al 2005,
HRT after Breast Cancer Three major Randomized trials HABITS (Hrt After Breast cancer Is iT Safe) - 345 women, mean age 55, 2.1year follow up Stockholm trial - 378 women, median age 56, 4.1 year follow up LIBERATE - 3098 women, median age 53, 3 year follow up
HRT after Breast Cancer HABITS: Median follow up 2.1 years RR of breast cancer 3.5 (1.5-8.1) 26% node positive 21% tamoxifen use Most using continuous combined HT STOCKHOLM: Median follow up 4.1 years RR of breast cancer 0.82 (0.35 1.9) 16% node positive 52% tamoxifen use 73% Estrogen only or long cycle (3/12) progestin Holmberg L Lancet 2004;363:453-4, von Schoultz E J Natl Canc Inst 2005;97:533-5
Breast Cancer recurrence (I.T.T) HR Livial v Placebo (95% CI) HR = 1.40 95% CI: 1.14-1.70 Kenemans P et al Lancet Oncology 2009;10:135-146
Hormone therapy in women at high risk of breast cancer Family history has no additive impact on breast cancer risk with HRT use1,2 although women with gene mutations are at vastly increased lifetime risk of breast cancer HRT use and family history had independent and non interacting risk factors for breast cancer in WHI3 Long term observational studies have reported no extra risk for those using HRT with a family history of breast cancer HRT following risk reduction surgery appears not to increase risk4,5 HRT in such women should use minimal progestrogen and ideally progesterone or dydrogesterone 1. Rippy L Marsden J Climacteric 2006;9:404-15 2. Sellars T et al Ann Intern Med 1997;127:973-80 3. Gramling R et al Epidemiology 2009;20:752-6 4. Rebeck T et al J Clin Oncol 2005;23:7804-10 5. Eisen J et al J Nat Cancer Inst. 2008;100:1361-67
Cognitive Behavior Therapy No change in digital thermography Reduces troublesomeness of vasomotor symptoms by >50% in breast cancer patients Side effects Improved mood Reduced anxiety Mann et al, 2012, Ayres et al 2012
Managing Menopause in high risk women USING THE EVIDENCE TO GUIDE PRACTICE
Clinical Guidance: Managing Menopause in high risk women Provide information about menopause and its management prior to chemotherapy Try and work out what is causing the hot flushes you may need to use several interventions For troublesome VMS start with SNRI or Gabapentin Consider increasing gabapentin at night if sleep disturbance Most work within a week Use non-pharmacological methods (CBT/mindfulness) to reduce impact Hickey et al 2008, 2012, Finch and Narod 2013, van Oostrom et al 2003, Scott et al, In press, Haines et al NAMS
Managing menopausal symptoms after breast cancer Attention to life style factors Avoid alternative therapies and practitioners Liason with Surgeon / Oncologist / GP Reduce dose of adjuvant therapy Vaginal lubricants, moisturisers or Oestriol ( Ospemifene C/I) Clonidine, SSRI / SNRI, Gabapentin Stellate Ganglion Block, Cognitive Behavioural Therapy Hickey M, Baber R Drug Safety 2005;28: 1085-1100 MacLennan A H Climacteric 2011;14:209-17
Model of multidisciplinary care: Menopause Symptoms After Cancer Clinic (MSAC) Patient referred to MSAC Clinic Assessment Treatment plan Patient seen by menopause specialist Information Patient seen by nurse specialist Evidence-based Clinical guidelines Management Issues resolved by Multidisciplinary team Data collection Hickey et al 2008, 2010, Marino et al 2013, Marino et al 2014
