Dr Sally Hope presents NICE Guideline 23 on the menopause and the recommendations for managing short-term menopause symptoms
Read this article to learn more about:
- diagnosing the menopause
- specific treatment options for women with premature ovarian insufficiency and women with, or at high risk of, breast cancer
- best practice for women stopping or starting HRT, including those at increased risk of venous thromboembolism.
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T he menopause, or perimenopause, is a time in a woman's life when she needs information to understand the physiological changes her body is experiencing, and possibly help in ameliorating the associated symptoms. The menopause occurs when a woman stops menstruating and reaches the end of her natural reproductive life, defined as 'when a woman has not had a period for 12 consecutive months (for women reaching menopause naturally).1 The perimenopause (also known as the menopausal transition or climacteric) is the period before the menopause in which the woman has irregular cycles of ovulation and menstruation leading up to menopause and continuing until 12 months after her final period. The average age of women reaching the menopause is 50 years and 9 months, but it occurs around 2–3 years earlier in women who smoke. About 33% of women have no, or very few, symptoms while some women experience hot flushes into their eighties.2
Box 1: NICE Accreditation Mark
NICE Guideline 23 on Menopause: diagnosis and management has been awarded the NICE Accreditation Mark.
See evidence.nhs.uk/accreditation for further details.
NICE Guideline 23
In November 2015, NICE Guideline (NG) 23 on Menopause: diagnosis and management1 was published (see Boxes 1 and 2, above). The guideline describes information and advice that patients can expect from their healthcare provider.1 NICE has also produced a specific version of the guideline for patients going through the menopause. This can be found in the 'Information for the public' section.3 Further sources of information for patients and carers can be found in Box 3, below
Box 3: Sources of advice about menopause and support for patients, their families, and/or carers
There is an enormous amount of information covered in the short, 29-page version of the guideline, such as a table on the additional risk of breast cancer associated with combined hormone replacement therapy (HRT) or oestrogen alone (see Table 1, below), as well as tables showing rates of coronary heart disease and stroke with and without HRT (combined or oestrogen alone).1 NICE Guideline 23 is an excellent, clear new resource summarising the current data: it can be printed off, laminated, and left in the waiting room for people to read.
|Difference in breast cancer incidence per 1000 menopausal women over 7.5 years (95% confidence interval) (baseline population risk in the UK over 7.5 years: 22.48 per 1000*)|
|Current HRT users||Treatment duration <5 years||Treatment duration 5–10 years||>5 years since stopping treatment|
|Women on oestrogen alone||RCT estimate†||4 fewer (-11 to 8)||No available data||No available data||5 fewer (-11 to 2)|
|Observational estimate‡||6 more (1 to 12)§||4 more (1 to 9)||5 more (-1 to 14)||5 fewer (-9 to -1)|
|Women on oestrogen + progestogen||RCT estimate†||5 more (-4 to 36)||No available data||No available data||8 more (1 to 17)|
|Observational estimate‡||17 more (14 to 20)||12 more (6 to 19)||21 more (9 to 37)||9 fewer (-16 to 13)||
Many of the recommendations for GPs are about giving information, and making sure that women understand the risks and benefits of treating or not treating with a wide variety of different options.1 Information should be offered throughout the care pathway, as shown in the algorithm in Figure 1 (see below). Information and advice that should be offered to menopausal women and their family members or carers (as appropriate) is shown in Box 4 (see below).
Box 4: Information and advice1
- Give information to menopausal women and their family members or carers (as appropriate) that includes:
- an explanation of the stages of menopause
- common symptoms and diagnosis
- lifestyle changes and interventions that could help general health and wellbeing
- benefits and risks of treatments for menopausal symptoms
- long-term health implications of menopause.
- Explain to women that as well as a change in their menstrual cycle they may experience a variety of symptoms associated with menopause, including:
- vasomotor symptoms (e.g. hot flushes and sweats)
- musculoskeletal symptoms (e.g. joint and muscle pain)
- effects on mood (e.g. low mood)
- urogenital symptoms (e.g. vaginal dryness)
- sexual difficulties (e.g. low sexual desire)
- Give information to menopausal women and their family members or carers (as appropriate) about the following types of treatment for menopausal symptoms:
- hormonal, e.g. HRT
- non-hormonal, e.g. clonidine
- non-pharmaceutical, e.g. CBT
- Give information on menopause in different ways to help encourage women to discuss their symptoms and needs
- Give information about contraception to women who are in the perimenopausal and postmenopausal phase. See guidance from the Faculty of Sexual & Reproductive Healthcare on contraception for women aged over 40 years
- Offer women who are likely to go through menopause as a result of medical or surgical treatment (including women with cancer, at high risk of hormone-sensitive cancer or having gynaecological surgery) support and:
- information about menopause and fertility before they have their treatment
- referral to a healthcare professional with expertise in menopause.
HRT=hormone replacement therapy; CBT=cognitive behavioural therapy
Adapted from: NICE. Menopause: diagnosis and management. NICE Guideline 23. NICE, 2015. Available at: www.nice.org.uk/guidance/ng23
Reproduced with permission
Health promotion advice
As well as information, health promotion advice should be offered to menopausal women throughout the care pathway (see Figure 1, above). Women are often open to opportune health promotion advice at this turning point in their lives. Indeed, one of the recommendations in NG23 is to 'give women advice on bone health and discuss these issues at review appointments,'1 helping to prevent osteoporosis, one of the long-term sequelae of the menopause, by making sure women are calcium and vitamin D replete.4
Another recommendation is to advise on 'lifestyle changes and interventions that could help general health and wellbeing,'1 as well as encouraging women to attend the national screening programmes (e.g. mammography and cervical screening).5
Diagnosing the menopause
For the vast majority of women aged over 45 years experiencing perimenopausal symptoms such as hot flushes and night sweats, the diagnosis is a clinical one (see Figure 1, above).1 Blood tests are not helpful, as the serum folliclestimulating hormone (FSH) fluctuates so wildly as to be useless. NICE Guideline 23 recommends that the following laboratory and imaging tests should not be used to diagnose perimenopause or menopause in women aged over 45 years: FSH, anti-Müllerian hormone, inhibin A, inhibin B, oestradiol, antral follicle count, or ovarian volume.1
Measuring two FSH levels on two occasions, 4–6 weeks apart, may be useful in women aged under 40 years with no or few periods (who should then be referred to specialist premature ovarian insufficiency clinics), or in women aged 40–45 years with menopausal symptoms.1
Managing short-term symptoms
A range of short-term symptoms are experienced by many women during the menopause and perimenopause. Common symptoms include vasomotor symptoms, effects on mood, and urogenital symptoms.6 Treatment should be adapted as needed based on a woman's changing symptoms, and each treatment should be reviewed at 3 months to assess efficacy and tolerability, and annually thereafter (unless there are clinical indications for an earlier review).1
Vasomotor symptoms, such as hot flushes and night sweats, can have a major impact on day-to-day activities. They are caused by constriction and dilatation of blood vessels in the skin that can lead to a sudden increase in blood flow to allow heat loss. Women experiencing vasomotor symptoms should be offered HRT after discussing the short-term and long-term benefits and risks. Women with a uterus should be offered preparations with oestrogen and progestogen; women without a uterus should be offered preparations with oestrogen alone.
Selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs) or clonidine should not be routinely offered as first-line treatment for vasomotor symptoms alone.1
There is some evidence for alternative therapies that may relieve vasomotor symptoms, such as isoflavones or black cohosh; however, it is important to explain to women that the preparations may vary, the safety of preparations is uncertain, and interactions with other medicines have been reported.1
Oestrogen deficiency can cause thinning and shrinking of the tissues of the vulva, vagina, urethra and bladder leading to multiple symptoms such as vaginal dryness, vaginal irritation, a frequent need to urinate, and urinary tract infections. Many women have the symptoms of vaginal dryness but do not want to take systemic HRT. Some women on systemic HRT may still have vaginal dryness and additional local vaginal oestrogens may be required.
Women with urogenital atrophy (including those on systemic HRT) should be offered vaginal oestrogen for as long as is needed to relieve symptoms.1 For women in whom HRT is contraindicated, vaginal oestrogen should be considered after seeking advice from a healthcare professional with expertise in the menopause.1
Consider increasing the dose of vaginal oestrogen (after seeking advice from a healthcare professional with expertise in the menopause) if vaginal oestrogen does not relieve symptoms. Moisturisers and lubricants may also provide a useful adjunct to vaginal oestrogen in those whose symptoms are not fully resolved.1
Starting and stopping HRT
Many women decide not to take HRT, and opt instead for non-pharmacological and/or non-hormonal measures.6 Cognitive behavioural therapy may help to alleviate low mood or anxiety that arises as a result of the menopause.1
NICE Guideline 23 recommends: 'consider transdermal rather than oral HRT for menopausal women who are at increased risk of VTE, including those with a BMI over 30 kg/m2'1 since 'the risk associated with transdermal HRT given at standard therapeutic doses is no greater than baseline population risk.'1 Also: 'consider referring menopausal women at high risk of VTE (for example, those with a strong family history of VTE or a hereditary thrombophilia) to a haematologist for assessment before considering HRT.'1
Unscheduled vaginal bleeding is a common side-effect within the first 3 months of HRT and should be reported at the 3-month review appointment, or promptly if it occurs soon after, in line with recommendations on endometrial cancer in NG12 on Suspected cancer: recognition and referral.7 Women who are stopping HRT should be given the choice between gradually reducing or immediately stopping, and it should be explained to them that:1
- gradually reducing HRT may limit recurrence of symptoms in the short term
- gradually reducing or immediately stopping HRT makes no difference to their symptoms in the longer term.
NICE Guideline 23 encourages an 'individualised approach at all stages of diagnosis, investigation, and management of menopause.' The full guideline6 has specific sections on the 'normal' menopause and its treatments, plus sections on premature ovarian insufficiency, and a separate consideration of women with breast cancer who have contraindications to hormonal therapy. This includes an in-depth look at the evidence regarding non-hormonal (selective serotonin reuptake inhibitors [SSRIs], serotonin and norepinephrine reuptake inhibitors [SNRIs], gabapentin, clonidine, St John's wort) and non-pharmacological interventions (cognitive behavioural therapy [CBT], acupuncture, exercise, relaxation therapies, mindfulness). There are also recommendations for future research in this area.
Premature ovarian insufficiency
Premature ovarian insufficiency (menopause occurring before the age of 40 years) can occur naturally or as a result of medical or surgical treatment. If a woman aged under 40 years presents with irregular periods or amenorrhoea, then premature ovarian insufficiency must be considered in the differential diagnosis. The woman's clinical and family history should be considered, and the diagnosis should be based on:1
- menopausal symptoms, including no or infrequent periods (taking into account whether the woman has a uterus) and
- elevated FSH levels on two blood samples taken 4–6 weeks apart.
Unless contraindicated, women diagnosed with premature ovarian insufficiency should be offered a sex steroid replacement, with a choice of HRT or a combined hormonal contraceptive.1 After the diagnosis has been confirmed, explain to women with premature ovarian insufficiency:1
- the importance of starting hormonal treatment either with HRT or a combined hormonal contraceptive and continuing treatment until at least the age of natural menopause (unless contraindicated)
- that the baseline population risk of diseases such as breast cancer and cardiovascular disease increases with age and is very low in women aged under 40
- that HRT may have a beneficial effect on blood pressure when compared with a combined oral contraceptive
- that both HRT and combined oral contraceptives offer bone protection
- that HRT is not a contraceptive.
Women with premature ovarian insufficiency and contraindications to hormonal treatments (for example, women with hormone-sensitive cancer) should be given advice on bone health, cardiovascular health, and symptom management.
Women with premature ovarian insufficiency often benefit from the multidisciplinary approach in a specialist clinic, to help them manage all aspects of physical and psychosocial health related to their condition.
Women with, or at high risk of, breast cancer
Breast cancer is the most common cancer in the UK with almost 51,000 new cases recorded in women 2012, representing an approximate incidence rate of 157 per 100,000 women per year.8 Incidence of new diagnoses reaches a peak at around age 60 to 64 years, with approximately 6600 cases recorded for every 100,000 women per year in the UK (women aged 60–64 years).8
Recommendations for the treatment of menopausal women with breast cancer, or at high risk of breast cancer, are given in NICE Clinical Guideline (CG) 80 on Early and locally advanced breast cancer: diagnosis and treatment,9 and NICE CG164 on Familial breast cancer: classification, care and managing breast cancer and related risks in people with a family history of breast cancer.10 NICE Guideline 23 also suggests that menopausal women with, or at high risk of, breast cancer should be offered:
- information on all available treatment options [that are not contraindicated for that individual]
- information that the SSRIs paroxetine and fluoxetine should not be offered to women with breast cancer who are taking tamoxifen
- referral to a healthcare professional with expertise in menopause.
In the full guideline, St John's wort is discussed as a treatment for symptomatic women with breast cancer.6 This is reflected in a recommendation that women with a history of, or at high risk of, breast cancer should be advised that St John’s wort may be a treatment option for the relief of vasomotor symptoms, while highlighting the uncertainty about appropriate dosages, persistence of effect, variation in the nature and potency of preparations, and the possibility of multiple drug interactions.1 St John's wort's induction of CYP2C9 means that it may interact with tamoxifen.11 Paroxetine and fluoxetine have been shown to cause long-term CYP2D2 inhibition during tamoxifen treatment, but venlafaxine or citalopram have no recorded interactions with tamoxifen.12
The menopause is a very complex transition into a new phase of life. Women need to understand the pros and cons of all possible treatment options to make their own individualised, evidence-based decision. Each woman must be considered as an individual, and a woman's ideas, concerns, and beliefs may change as she progresses through this transition. It is an ideal opportunity for the primary care team to promote and assist each woman achieve a healthier lifestyle for her future.
- Information and health promotion advice should be offered to menopausal women throughout the care pathway
- An individualised approach should be adopted at all stages of diagnosis, investigation, and management of menopause
- For women over 45 years, diagnosis of the menopause is clinical:
- FSH, anti-Müllerian hormone, inhibin A, inhibin B, oestradiol, antral follicle count, or ovarian volume should not be used to diagnose the menopause
- Short-term symptoms of the menopause are common and the treatments are varied:
- treatment should be adapted as needed, based on the woman’s changing symptoms
- women should be informed of the benefits and risks associated with HRT to allow them to make an informed choice about which treatment to use
- Women with, or at high risk of breast cancer, and women with premature ovarian insufficiency may benefit from referral to a healthcare professional with expertise in the menopause.
FSH=follicle-stimulating hormone; HRT=hormone replacement therapy
GP commissioning messages
written by Dr David Jenner, GP, Cullompton, Devon
- NG23 is designed to clarify the risks and benefits of HRT for both patients and healthcare professionals
- For commissioners, the guidance specifies the need for a 'healthcare professional with expertise in menopause' for specialist advice:
- CCGs should consider if this role could be fulfilled by a GPwSI in many cases to avoid the need for secondary-care referral and associated PbR costs
- It is difficult to scope whether this guidance will have any effect on the overall prescription rate for HRT but it is likely to drive increased prescribing of topical rather than systemic therapy, and formularies should reflect where topical agents provide fewer risks
- The tables in the guidance detailing the risks and benefits of HRT do not appear to be easily accessible to the public and other sources of such information like the BNF may be useful to use alongside NG23:
- CCGs could consider developing their own, easy to understand tables and publishing these on formulary websites
- Empowering patients to make personal choices is key to the implementation of NG23 and this requires clear explanation of absolute and relative risk.
NG=NICE Guideline; HRT=hormone replacement therapy; GPwSI=GP with a special interest; PbR=payment by results; BNF=British National Formulary
Read the Guidelines summary of NG23 on Menopause: diagnosis and management for more information on managing menopause in primary care
- NICE. Menopause: diagnosis and management. NICE Guideline 23. NICE, 2015. Available at: www.nice.org.uk/guidance/ng23
- Rees M, Purdie D, Hope S. The menopause: what you need to know. Marlow: British Menopause Society, 2006.
- NICE. Menopause: Information for the public. NICE Guideline 23: IFP. NICE, 2015. Available at: www.nice.org.uk/guidance/ng23/ifp/chapter/menopause
- NICE. Osteoporosis—prevention of fragility fractures. NICE Clinical Knowledge Summaries. NICE, 2015. Available at: cks.nice.org.uk/osteoporosis-prevention-of-fragility-fractures
- NICE. NICE Clinical Knowledge Summaries. Menopause. NICE, 2015. Available at: cks.nice.org.uk/menopause
- NICE. Full guideline: Menopause. NICE Clinical Guideline: Methods, evidence and recommendations. NICE, 2015. Available at: www.nice.org.uk/guidance/ng23/evidence/full-guideline-559549261
- NICE. Suspected cancer: recognition and referral. NICE Guideline 12. NICE, 2015. Available at: nice.org.uk/guidance/ng12
- Cancer Research UK. Breast cancer incidence (invasive) statistics. www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/breast-cancer/incidence-invasive (accessed 4 February 2016).
- NICE. Early and locally advanced breast cancer: diagnosis and treatment. NICE Clinical Guideline 80. NICE, 2009. Available at: www.nice.org.uk/guidance/cg80
- NICE. Familial breast cancer: classification, care and managing breast cancer and related risks in people with a family history of breast cancer. NICE Clinical Guideline 164. NICE, 2013. Available at: www.nice.org.uk/guidance/cg164
- Medicines and Healthcare products Regulatory Agency. Other medicines which may interact with St John's wort. London: MHRA, 2000. Available at: www.mhra.gov.uk/home/groups/comms-ic/documents/websiteresources/con019566.pdf
- Binkhorst L, Mathijssen R, van Herk-Sukel M et al. Unjustified prescribing of CYP2D6 inhibiting SSRIs in women treated with tamoxifen. Breast Cancer Res Treat 2013; 139 (3): 923–929. G