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Menopause - Management
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Overview of management

  • Assess the stage of the menopause to determine whether the woman is perimenopausal, postmenopausal, or has a premature menopause (less than 45 years of age).
  • Assess the symptoms and their severity: (e.g. hot flushes, night sweats, vaginal dryness).
  • Refer women if they:
    • Present with clinical features suggestive of cervical or endometrial cancer.
    • Are less than 40 years of age at presentation.
    • Would like hormone replacement therapy (HRT) but have a contraindication to it (e.g. current of past breast or endometrial cancer).
  • Offer lifestyle advice to all women with menopausal symptoms.
  • Offer treatment with (HRT) if, the woman has been given advice about the risks and benefits of HRT, has no contraindications to HRT and would like treatment. See:
  • Offer alternative treatments with antidepressants or clonidine if HRT is inappropriate, see Management without HRT.
  • Offer HRT or the combined oral contraceptive pill if the woman is younger than 45 years old, see Management of premature menopause.

How should I assess a woman with menopausal symptoms?

  • Assess the stage of the menopause:
    • Ask the woman if she is still having periods, to determine whether she is perimenopausal or postmenopausal:
      • If her periods have stopped, record when the last period occurred.
      • If the woman is still having periods, ask about their frequency, heaviness, and duration.
    • Determine if the woman is less than 45 years of age (premature menopause):
  • Assess the symptoms and their severity:
    • Ask which symptoms the woman has, to determine if they would be likely to respond to hormone replacement therapy (HRT) (e.g. hot flushes, night sweats, vaginal dryness), or whether other treatments may be more suitable (e.g. treatment for primary depression or primary insomnia).
    • Determine the severity of the symptoms and the extent to which they are affecting the woman's life.
  • Assess the risk of cardiovascular disease:
    • Women with cardiovascular disease or at increased risk of cardiovascular disease should have their cardiovascular risk factors managed — see the CKS topic on CVD risk assessment and management.
  • Assess the risk of osteoporosis:
  • Discuss the woman's expectations:
    • Ask why she has consulted (e.g. concern regarding the cause of the symptoms).
    • Ask if she would like treatment for her symptoms.
  • Assess what type of treatment may be appropriate:
    • Ask the woman if she would like treatment with HRT or without HRT.
    • For women who would like HRT, check that they are suitable for treatment:
      • Ask if they have any contraindications to HRT (e.g. history of breast cancer, venous thromboembolism).
      • Discuss the risks and benefits of HRT.
      • Record body mass index and blood pressure.
      • Breast examination is not routinely necessary, however the national mammography screening programme and personal breast awareness must be discussed before starting HRT.
      • Pelvic examination is not routinely required unless clinically indicated (past or current disease, symptoms, or family history).
      • Investigations are not routinely indicated.
      • See Managing symptoms with HRT.
    • For women who are not suitable for treatment with HRT (e.g. those who have contraindications to HRT) or do not want to use HRT, see Managing symptoms without HRT.
  • Encourage all women to participate in the national cervical screening programme.
Clarification / Additional information
  • The following are all contraindications to starting hormone replacement therapy:
    • Hormone-dependent cancer (e.g. endometrial cancer, current or past breast cancer).
    • Active or recent arterial thromboembolic disease (e.g. angina or myocardial infarction).
    • Venous thromboembolic disease, pulmonary embolism, or current pregnancy.
    • Severe active liver disease.
    • Undiagnosed breast mass.
    • Uninvestigated abnormal vaginal bleeding.
  • Investigations are not routinely indicated before starting hormone replacement therapy unless:
    • There is sudden change in menstrual pattern, intermenstrual bleeding, postcoital bleeding, or postmenopausal bleeding: consider doing an endometrial assessment.
    • There is a personal or family history of venous thromboembolism: consider doing a thrombophilia screen.
    • There is a high risk of breast cancer: mammography or MRI may be considered (as appropriate for the woman's age).
    • The woman has arterial disease or a high load of other risk markers for arterial disease: a lipid profile may be useful.
Basis for recommendation

When should I refer?

  • Refer urgently if the woman presents with clinical features suggestive of cervical or endometrial cancer:
    • Abnormal bleeding (postcoital bleeding, unscheduled vaginal bleeding, especially if heavy, prolonged, or recurrent or a sudden change in menstrual pattern).
    • Postmenopausal bleeding.
    • Persistent intermenstrual bleeding and negative pelvic examination.
    • A palpable abdominal or pelvic mass (refer urgently for ultrasonography).
  • Refer to secondary care women:
    • Who are less than 40 years of age at presentation.
  • Seek specialist advice if a woman would like hormone replacement therapy but has a contraindication to it:
    • Hormone-dependent cancer (e.g. endometrial cancer, current or past breast cancer).
    • Active or recent arterial thromboembolic disease (e.g. angina or myocardial infarction).
    • Venous thromboembolic disease, pulmonary embolism.
    • Current pregnancy.
    • Severe active liver disease.
    • Undiagnosed breast mass.
    • Uninvestigated abnormal vaginal bleeding.
Basis for recommendation
  • These recommendations are based on published expert opinion [Waller and McPherson, 2003; Monga, 2006; Rees and Purdie, 2006b].
  • The National Institute for Health and Clinical Excellence recommends urgent referral for all women presenting with alarm symptoms of gynaecological cancer [NICE, 2005].
  • Women who are less than 40 years of age require investigations to determine the cause of a premature menopause (e.g. primary ovarian failure) and to discuss fertility if appropriate.

What lifestyle advice can I give for menopausal symptoms?

  • Encourage all women to make lifestyle modifications to reduce menopausal symptoms:
    • Hot flushes and night sweats:
      • Take regular exercise, wear lighter clothing, sleep in a cooler room, and reduce stress.
      • Avoid possible triggers, such as spicy foods, caffeine, smoking, and alcohol.
    • Sleep disturbances:
      • Avoiding exercise late in the day and maintaining a regular bedtime can improve sleep.
    • Mood and anxiety disturbances:
      • Adequate sleep, regular physical activity, and relaxation exercises may help.
    • Cognitive symptoms:
      • Exercise and good sleep hygiene may improve subjective cognitive symptoms.
Basis for recommendation
  • These recommendations are based on published expert opinion [ICSI, 2006; Rees and Purdie, 2006a].
  • There is evidence that smoking cigarettes and having a body mass index of more than 30 kg/m2 increases the likelihood of flushing.
  • From observational studies, there are more reports of positive effects of exercise on hot flushes than reports of negative effects or mixed findings. Therefore, regular exercise might positively influence the frequency and severity of vasomotor symptoms in menopausal women [Daley et al, 2006].

How should I manage menopausal symptoms with HRT?

What issues should I discuss with a woman before starting HRT?

  • Before starting hormone replacement therapy (HRT), discuss:
    • The benefits and possible risks of hormone replacement therapy or tibolone (if appropriate).
    • The expected duration of therapy:
      • For vasomotor symptoms, most women require 2–3 years of therapy, but some women may need longer. This judgement should be made on a case-by-case basis with regular attempts to discontinue. Symptoms may recur for a short time after stopping HRT [MHRA and CHM, 2007b].
      • Topical (vaginal) oestrogen may be required long term. In some women symptoms may recur once treatment has stopped [Rees and Purdie, 2006a].
      • Women with premature menopause usually take hormone replacement therapy up to the age of the natural menopause (50 years); at that time, therapy is usually reassessed.
    • Any possible adverse effects, such as breast tenderness or enlargement, nausea, headaches, or bleeding.

What advice should I give about the benefits of HRT?

  • Advise the woman that hormone replacement therapy (HRT) is effective for:
    • Treating vasomotor symptoms (e.g. hot flushes and night sweats).
    • Treating urogenital symptoms (e.g. vaginal dryness, dyspareunia as a result of vaginal dryness, recurrent urinary tract infections, and urinary frequency and urgency).
    • Sleep or mood disturbances caused by hot flushes and night sweats.
    • Preventing osteoporosis. HRT is not normally used as a first-line treatment (as the risks outweigh the benefits) except in women with premature ovarian failure.
    • Reducing the risk of colorectal cancer (but hormone replacement therapy is currently not recommended for this use).
Basis for recommendation
  • These recommendations are based on expert opinion from the published literature, as well as systematic reviews and large randomized controlled trials [NZGG, 2004; BMS, 2006a; ICSI, 2006; Rees and Purdie, 2006a; MHRA and CHM, 2007b].
  • Hot flushes and night sweats:
    • Good evidence indicates that oral, or transdermal hormone replacement therapy (HRT), used as oestrogen alone or oestrogens combined with progestogens, is highly effective for reducing the frequency and severity of hot flushes and night sweats caused by the menopause.
  • Vaginal atrophy (dryness and dyspareunia):
    • There is evidence that HRT preparations (combined oral and transdermal oestrogens and progestogens, or intravaginal oestrogens) are effective for treating vaginal atrophy (dryness, burning and itching, and dyspareunia).
  • Recurrent urinary tract infections:
    • There is evidence that oral and intravaginal oestrogen is effective for preventing urinary tract infections. The appropriate dose and duration of therapy have not been established. Long-term treatment may be required because symptoms recur when treatment is stopped [Rees and Purdie, 2006a].
  • Sleep disturbances:
    • By alleviating night sweats, HRT often improves sleep. Women often report an improvement in sleep patterns with HRT even if hot flushes or night sweats are not prominent menopausal symptoms [ICSI, 2006]. There is evidence that combined oral oestrogen and progestogen therapy provides a small statistical but not clinically meaningful improvement in sleep disturbances.
  • Incontinence:
    • The British Menopause Society currently recommends the use of systemic or topical oestrogen for urinary frequency and urgency [BMS, 2006a]. The evidence to support the use of oestrogens is conflicting. A Cochrane systematic review found evidence that oestrogen treatment improved or cured incontinence; this was more likely with urge incontinence [Moehrer et al, 2003]. However, a subsequently published analysis of the Women's Health Initiative trial found that oestrogen therapy alone and combined with progestogen therapy increased the risk of urinary incontinence among continent women and worsened urinary incontinence among symptomatic women after 1 year [Hendrix et al, 2005].
  • Mood disorders:
    • No evidence indicates that HRT has a direct effect on mood, irritability, or anxiety. However, HRT may be helpful if other menopausal symptoms, such as hot flushes and sleep disturbance, are present [ICSI, 2006].
  • Libido:
    • Other than relieving hot flushes and improving sleep, HRT improves urogenital atrophy, thinning, dryness, and loss of elasticity, all of which may cause dyspareunia. While this may improve sexual functioning for many women, HRT has no proven direct benefit on sexuality or libido [ICSI, 2006].
  • Osteoporosis:
  • Colorectal cancer:
    • There is evidence that HRT reduces the risk of colorectal cancer [Writing Group for the Women's Health Initiative Investigators, 2002].
    • The risk of colorectal cancer increases with increasing age. Therefore, HRT produces a greater potential reduction in the number of cases of colorectal cancer in older women than in younger women. However, some of the potential risks of HRT also increase with age. Little is known about colorectal cancer risk when treatment is stopped. No information is available about HRT in high-risk populations, and current evidence does not allow recommendation of HRT to prevent colorectal cancer [BMS, 2006a].
  • Use of HRT may be associated with reduced tooth loss, reduced incidence of age-related macular degeneration and cataracts, improved faecal continence, improved wound healing, and improved balance. However, HRT is not licensed for these indications, and the risks of prescribing HRT for any of these problems are likely to outweigh the benefits.

What advice should I give about the possible risks of HRT?

  • Advise the woman that there is a small increase in risk for:
    • Breast cancer.
    • Endometrial cancer.
    • Ovarian cancer.
    • Venous thromboembolism (deep vein thrombosis or pulmonary embolism).
    • Coronary heart disease for women who have started combined therapy more than 10 years after menopause.
    • Stroke.
Clarification / Additional information
  • The number of additional cases (compared with the background risk) of cancer and cardiovascular conditions in hormone replacement therapy users is discussed in Risks of HRT.
Basis for recommendation
  • The Medicines and Healthcare products Regulatory Agency (MHRA) and its independent adviser, the Commission on Human Medicines, have reviewed the safety data for hormone replacement therapy (HRT). The above recommendations are based on this safety review [MHRA and CHM, 2007b]. The MHRA found the following:
    • Breast cancer:
      • Combined HRT has been associated with the highest risk. The risk is lower with oestrogen-only HRT than with combined HRT.
      • Risk increases with duration of use and returns to baseline within 5 years of stopping treatment.
    • Endometrial cancer:
      • In women with a uterus, oestrogen-only HRT substantially increases the risk of endometrial hyperplasia and carcinoma in a dose- and duration-dependent manner.
      • Addition of progestogen cyclically for at least 10 days per 28-day cycle greatly reduces the risk, and addition of progestogen every day eliminates the risk.
    • Ovarian cancer:
      • Long-term use of oestrogen-only or combined HRT may be associated with a small increased risk of ovarian cancer. This risk returns to baseline a few years after stopping treatment.
    • Venous thromboembolism (deep vein thrombosis or pulmonary embolism):
      • The risk is higher with combined HRT than with oestrogen-only HRT, and events are more likely in the first year of use.
      • The level of risk associated with other routes of administration has not been clearly established, although it may be lower with transdermal HRT.
    • Stroke:
      • In randomized controlled trials, oestrogen-only and combined HRT increased the risk of stroke (mostly ischaemic) compared with placebo. Although the increase in relative risk seems to be similar irrespective of age, baseline risk of stroke increases with age and therefore older women have a greater absolute risk. Limited observational data suggest that this risk may depend on oestrogen dose.
    • Cognitive effects:
      • There is evidence that for women who start HRT after 65 years of age, conjugated equine oestrogen does not protect against mild cognitive impairment or probable dementia. Evidence suggests that combined HRT (conjugated equine oestrogen and medroxyprogesterone acetate) may increase the risk of dementia in women more than 75 years of age. The MHRA have advised that HRT not be prescribed for preventing a decline in cognitive function [CSM, 2004a].
  • Coronary heart disease (CHD):
    • No increased risk of CHD with the use of oestrogen-only HRT has been identified to date. Importantly, there are no data from randomized controlled trials to suggest a cardiovascular benefit with oestrogen-only or combined HRT [MHRA and CHM, 2007b].
    • Randomized controlled trials have found an increased risk of CHD in women who started combined (oestrogen-progestogen) therapy more than 10 years after menopause. Very few randomized controlled trials have assessed younger, newly menopausal women, and some have suggested a lower relative risk in these women compared with older women. The low baseline risk of CHD in most younger women, and the very low attributable risk due to HRT, means that their overall CHD risk is likely to be low.
    • For a more detailed discussion on the role of hormone replacement therapy and coronary heart disease in women see the website for the MHRA.

What advice should I give about the risks and benefits of tibolone?

  • Advise the woman that tibolone is effective for treating vasomotor symptoms and reduces the risk of spine fractures. It may also improve sexual functioning.
  • Tibolone is associated with a small increased risk of stroke.
  • Most studies have shown a small increased risk of having endometrial cancer diagnosed with tibolone use.
  • Limited data suggest that tibolone may be associated with a small increased risk of breast cancer, and that tibolone does increase the risk of breast cancer recurrence in women with a history of breast cancer.
  • In younger women, the risk profile of tibolone is broadly similar to that for conventional combined hormone replacement therapy.
  • For women more than about 60 years of age, the risks associated with tibolone start to outweigh the benefits because of the increased risk of stroke.
Basis for recommendation
  • These recommendations are based on randomized controlled trials and a recently published assessment of the benefit–risk balance published by the Medicines and Healthcare products Regulatory Agency (MHRA) [MHRA and CHM, 2007a; MHRA, 2009].
  • The MRHA assessed the balance of benefits and risks for tibolone after the Long-term Intervention on Fractures with Tibolone (LIFT) study was terminated because of an increased risk of stroke in those assigned tibolone compared with those assigned placebo. The main results of this assessment were as follows:
    • Stroke:
      • The LIFT study identified a significantly (2.2-times) increased risk of stroke, mostly ischaemic, in tibolone users; risk increased from the first year of treatment. Baseline risk of stroke is strongly age-dependent, and the absolute risk with tibolone therefore increases with older age.
      • Randomized controlled trials have identified an approximate 1.3-times increase in stroke risk with combined hormone replacement therapy (HRT).
    • Breast cancer:
      • There are limited clinical trial data for breast cancer risk in healthy women. However, the LIBERATE study in women with previous breast cancer was stopped because it could not establish non-inferiority of tibolone compared with placebo.
      • The Million Women Study identified a significantly increased risk of breast cancer in tibolone users (relative risk [RR] 1.5, 95% CI 1.3 to 1.7), which is similar to that for oestrogen-only HRT (RR 1.3, 95% CI 1.2 to 1.4) and significantly lower than that for combined HRT (RR 2.0, 95% CI 1.9 to 2.1). Risk increased with longer duration of use and returned to baseline within a few years of stopping treatment.
    • Venous thromboembolism:
      • The few data available do not suggest an increased risk of venous thromboembolism compared with combined HRT users or with non-users.
    • Coronary heart disease:
      • No conclusions can be drawn from the available data. In view of the increased risk of stroke associated with tibolone, an increase in coronary events is biologically plausible. In studies, tibolone caused a marked dose-dependent decrease in high-density lipoprotein cholesterol levels (–22.4% after 2 years); total triglyceride and lipoprotein (a) levels were also reduced. A decrease in total cholesterol and very low-density lipoprotein cholesterol levels was not dose dependent, and low-density lipoprotein cholesterol levels did not change. The clinical implication of these findings is not yet known.
  • Endometrial cancer: The MHRA have reviewed the evidence on effects of tibolone on the endometrium and have concluded that:
    • Most studies show an increased risk of having endometrial cancer diagnosed associated with use of tibolone.
    • Despite the lack of evidence for an association between tibolone and endometrial cancer from pharmacological studies and the 2 year Tibolone Histology of the Endometrium and Breast Endpoints Study (THEBES), two large epidemiological studies have identified a significant increase in the risk of endometrial cancer in association with tibolone use that increased with increasing duration of use. A higher incidence of endometrial cancer was reported in older women given tibolone in the LIFT study compared with placebo. These women also experienced an increase in incidence of endometrial double wall thickness, measured by vaginal ultrasonography, compared with placebo.
    • Although a causal relation has not been proven, women who are prescribed tibolone have an increased risk of having endometrial cancer diagnosed than both never-users and users of combined HRT. The reason for this increase is not clear.
  • For more detailed information, see the MHRA website.

How should I manage perimenopausal women with HRT (intact uterus)?

How should I manage peri-menopausal women with HRT (intact uterus)?

  • Offer lifestyle advice.
  • Advise about the risks and benefits of hormone replacement therapy (HRT) and record this in her notes.
  • Urogenital symptoms alone (e.g. vaginal dryness, dyspareunia, recurrent urinary tract infections, or urinary frequency and urgency):
    • Offer treatment with low-dose vaginal oestrogen (cream, pessary, tablet, or ring) or systemic (oral or transdermal) cyclical combined HRT:
      • Low-dose vaginal oestrogen may be preferred if the woman does not wish to take systemic HRT or cannot tolerate systemic HRT.
      • For women with infrequent periods or who cannot tolerate progestogens, a 3-monthly regimen may be preferred.
  • Vasomotor symptoms (e.g. hot flushes, night sweats) with or without urogenital symptoms:
    • Offer systemic (oral or transdermal) cyclical combined HRT:
      • For women with infrequent periods or who cannot tolerate progestogens, a 3-monthly regimen may be preferred.
  • For a full discussion on the choice of HRT preparations, see Type of product to offer.
  • Advise the woman that she may still become pregnant if contraception is not used:
    • A suitable method of contraception should be used for 1 year after the last menstrual period if the woman is more than 50 years of age, or for 2 years after the last menstrual period if the woman is less than 50 years of age.
    • See the CKS topic on Contraception for a detailed discussion on the most appropriate method of contraception in perimenopausal women and for how long it should be continued.
Clarification / Additional information
  • Prescribe hormone replacement therapy at the lowest effective dose for the shortest duration possible.
  • Maximal benefit of systemic hormone replacement therapy is usually seen within 3 months, and treatment is generally continued for up to 5 years.
  • Urogenital symptoms: topical oestrogens should be used in the lowest effective amount to minimize systemic absorption. Treatment should be interrupted as least annually to re-assess the need for continued treatment. If breakthrough bleeding or spotting appears at any time on therapy, the reason should be investigated and may include endometrial biopsy to exclude endometrial malignancy. Long term treatment is often required as symptoms can recur on cessation of therapy.
Basis for recommendation
  • These recommendations are based on published expert opinion and evidence from systematic reviews and large randomized controlled trials [NZGG, 2004; ICSI, 2006; Rees and Purdie, 2006a; SOGC, 2006; MHRA and CHM, 2007b].
  • Vaginal oestrogens:
    • Low-dose oestrogen therapy is preferred because it incurs no adverse endometrial effects and a progestogen is not required for endometrial protection [Rees and Purdie, 2006a]. Vaginal oestrogen therapy may be required long-term, as symptoms recur when treatment is stopped. However the endometrial safety of long term or repeated use of topical vaginal oestrogens is uncertain [CSM, 2003b].
  • Systemic hormone replacement therapy (HRT):
    • Combined oestrogen and progestogen cyclical preparations are recommended in perimenopausal women because they produce predictable withdrawal bleeding, whereas continuous regimens often cause unpredictable bleeding [Rees and Purdie, 2006a].
    • Treatment for vasomotor symptoms should be continued for at least 1 year; otherwise, symptoms recur. Menopausal symptoms usually resolve within 2–5 years, but some women experience symptoms for many years, even into their seventies and eighties [Rees and Purdie, 2006a].
  • Contraception:
    • Hormone replacement therapy does not suppress ovulation and does not provide contraceptive cover.
  • Hot flushes and night sweats:
    • Good evidence indicates that oral and transdermal HRT with oestrogen alone or oestrogens combined with progestogens is highly effective for reducing the frequency and severity of hot flushes and night sweats caused by the menopause.
  • Vaginal atrophy (dryness and dyspareunia):
    • There is evidence that HRT (combined oral and transdermal [oestrogens and progestogens] or intravaginal oestrogens) is effective for treating vaginal atrophy (dryness, burning and itching, and dyspareunia).
  • Recurrent urinary tract infections:
    • There is evidence that oral and intravaginal oestrogen is effective for preventing urinary tract infections. The appropriate dose and duration of therapy have not been established, and long-term treatment is required because symptoms recur when treatment is stopped [Rees and Purdie, 2006a].
  • Sleep disturbances:
    • By alleviating night sweats, HRT often improves sleep. Women often report improvement in sleep patterns with HRT even if hot flushes or night sweats are not prominent menopausal symptoms [ICSI, 2006]. There is evidence that combined oral oestrogen and progestogen therapy provides a small statistical but not clinically meaningful improvement in sleep disturbances.
  • Incontinence:
    • The British Menopause Society currently recommend the use of oral or topical oestrogen for urinary frequency and urgency [BMS, 2006a]. The evidence to support the use of oestrogens is conflicting. A Cochrane systematic review found evidence that oestrogen treatment improved or cured incontinence; this was more likely with urge incontinence [Moehrer et al, 2003]. However, a subsequently published analysis of the Women's Health Initiative trial found that oestrogen therapy alone and combined with progestogen therapy increased the risk of urinary incontinence among continent women and worsened urinary incontinence among symptomatic women after 1 year [Hendrix et al, 2005].
  • Mood disturbances:
    • No evidence indicates that HRT has a direct effect on mood, irritability, or anxiety. However, HRT may be helpful if other menopausal symptoms, such as hot flushes and sleep disturbances, are present [ICSI, 2006].
  • Libido:
    • HRT improves urogenital atrophy, thinning, dryness, and loss of elasticity, all of which may cause dyspareunia. While this may improve sexual functioning for many women, HRT has no proven direct benefit on sexuality or libido [ICSI, 2006].
    • There is evidence that loss of libido can be improved by testosterone supplementation, particularly after surgical menopause. Treatment is not always successful, other factors such as marital problems may be involved, and testosterone may cause potentially serious adverse effects [Rees and Purdie, 2006a].
    • Testosterone patches are licensed for women with surgically induced menopause (in women receiving concomitant oestrogen therapy), but they are not recommended for women naturally menopausal or those taking conjugated oestrogens. Safety and efficacy of testosterone patches have not been established beyond 1 year of treatment [BNF 54, 2007].

When should I switch to a continuous combined preparation?

  • Consider switching from cyclical therapy to continuous combined therapy when the woman is considered to be postmenopausal. However, it may be difficult to decide when the woman is postmenopausal.
  • Women are generally considered to be postmenopausal if:
    • They are more than 54 years of age (it is estimated that 80% of women will be postmenopausal by this age).
    • They have had previous amenorrhoea or increased levels of follicle-stimulating hormone. Women who experienced 6 months of amenorrhoea or had increased follicle-stimulating hormone levels in their mid-40s are likely to be postmenopausal after taking several years of cyclical hormone replacement therapy.
Basis for recommendation

What follow up is required?

  • Review the woman 3 months after starting hormone replacement therapy (HRT) and once each year thereafter.
  • At the initial 3-month review:
    • Assess the effectiveness of treatment and adjust to achieve symptom control.
    • Enquire about any adverse effects and manage appropriately.
    • Enquire about bleeding patterns.
    • Check blood pressure and body weight.
  • Once each year:
    • Check effectiveness of treatment and adjust to achieve symptom control.
    • Check for adverse effects and manage appropriately.
    • Consider switching from cyclical HRT to continuous combined HRT, if appropriate.
    • Interrupt treatment with intravaginal oestrogen and consider stopping systemic HRT, to re-assess the need for continued use.
    • Explain that some of the risks (e.g. breast cancer, ovarian cancer) associated with HRT increase with longer duration of hormone replacement therapy (HRT):
      • Breast cancer: combined HRT increases this risk by about 1.6 times after 5 years of use and 2.3 times after 10 years of use. Risk decreases within a few years of stopping HRT.
      • Ovarian cancer: long-term use of oestrogen-only HRT and combined HRT may slightly increase the risk. Risk decreases after stopping HRT.
    • Perform a breast examination if indicated by personal or family history.
    • Encourage breast awareness and participation in the national breast screening programme as appropriate for their age.
    • Pelvic examination is required only if clinically indicated (e.g. if there is unscheduled bleeding, especially if heavy, prolonged, or recurrent).
    • Check blood pressure.
  • Oestrogen levels are rarely indicated.
Clarification / Additional information
  • Measurement of estradiol is rarely indicated but may be of use if the clinical response (i.e. symptomatic relief) to HRT is poor [Smellie et al, 2006]:
    • To establish whether absorption of transdermal HRT is adequate in women in whom poor absorption is suspected. If poor absorption is confirmed, prescribe oral HRT.
    • To ensure that oestrogen levels have fallen before implant replacement in women, to avoid supraphysiological concentrations and possible tachyphylaxis.
    • Rarely, in women with persisting symptoms where poor compliance is suspected.
Basis for recommendation
  • These recommendations are based on published expert opinion [Working Group on Breast and Pelvic Examination, 2001; RCPE, 2003; AACE Menopause Guidelines Revision Task Force, 2006; Rees and Purdie, 2006a; MHRA and CHM, 2007b; Roberts, 2007].
  • An initial review is recommended at 3 months, as most menopausal symptoms respond by then:
    • Vasomotor symptoms: improvement is usually noted within 4 weeks. Usually, hormone replacement therapy (HRT) is used for less than 5 years [BMS, 2006a].
    • Urogenital symptoms: topical oestrogens should be used in the lowest effective amount to minimize systemic absorption [CSM, 2003b]. However long term treatment is often required as symptoms can recur on cessation of therapy [BMS, 2006a]. Treatment should be interrupted as least annually to re-assess the need for continued treatment. If breakthrough bleeding or spotting appears at any time on therapy, the reason should be investigated and may include endometrial biopsy to exclude endometrial malignancy [CSM, 2003b].
  • An annual review is recommended because the risks and benefits of HRT for each woman change over time and need to be discussed regularly.
  • Blood pressure measurement is not routinely needed, but opportunistic screening is useful.
  • Measurement of follicle-stimulating hormone:
  • Measurement of oestrogen:
    • This recommendations is based on Best Practice in primary care pathology [Smellie et al, 2006].

When should I refer women who have started HRT?

  • Refer women who are taking cyclical hormone replacement therapy if:
    • There is a change in pattern of withdrawal bleeds or break through bleeding.
    • There is multiple treatment failure e.g. three or more regimens have been tried.
  • Refer to a team specializing in the management of gynaecological cancer (depending on local arrangements) any persistent or unexplained bleeding after cessation of hormone therapy for 6 weeks.
Basis for recommendation
  • These recommendations are based on published expert opinion [Monga, 2006; Rees and Purdie, 2006b].
  • Abnormal bleeding requires investigation if:
    • The pattern of withdrawal bleeding or breakthrough bleeding changes while taking monthly cyclical therapy.
    • There is breakthrough bleeding that persists for more than 4–6 months or does not lessen while taking a 3-monthly regimen.

How should I manage postmenopausal women with HRT (intact uterus)?

How should I manage post-menopausal women with HRT (intact uterus)?

  • Offer lifestyle advice.
  • Advise the woman about the risks and benefits of oestrogen-based hormone replacement therapy (HRT) or tibolone as appropriate and record this in her notes.
  • Urogenital symptoms alone (e.g. vaginal dryness, dyspareunia, recurrent urinary tract infections, or urinary frequency and urgency):
    • Offer treatment with low-dose vaginal oestrogen (cream, pessary, tablet or ring) therapy or systemic (oral or transdermal) continuous combined HRT:
      • Low-dose vaginal oestrogen may be preferred if the woman does not wish to take systemic HRT or cannot tolerate systemic HRT.
  • Vasomotor symptoms (e.g. hot flushes, night sweats), with or without urogenital symptoms:
    • Offer systemic (oral or transdermal) continuous combined HRT or tibolone.
  • If the woman requires treatment for decreased libido, consider offering tibolone (licensed use).
  • For a full discussion on the choice of HRT preparations, see Type of product to offer.
  • Give advice regarding contraception:
    • A suitable method of contraception should be used for 1 year after the last menstrual period if the woman is more than 50 years of age, or for 2 years after the last menstrual period if the woman is younger than 50 years of age.
    • See the CKS topic on Contraception for a detailed discussion on the most appropriate method of contraception in menopausal women and for how long it should be continued.
Clarification / Additional information
  • Prescribe hormone replacement therapy at the lowest effective dose for the shortest duration possible.
  • Maximal benefit of systemic hormone replacement therapy is usually seen within 3 months, and treatment is generally continued for up to 5 years.
  • Urogenital symptoms: topical oestrogens should be used in the lowest effective amount to minimize systemic absorption. Treatment should be interrupted as least annually to re-assess the need for continued treatment. If breakthrough bleeding or spotting appears at any time on therapy, the reason should be investigated and may include endometrial biopsy to exclude endometrial malignancy. Long-term treatment is often required as symptoms can recur on cessation of therapy.
Basis for recommendation
  • These recommendations are based on published expert opinion and evidence from systematic reviews and large randomized controlled trials [NZGG, 2004; ICSI, 2006; Rees and Purdie, 2006a; MHRA and CHM, 2007b].
  • Vaginal oestrogens:
    • Low-dose oestrogen therapy is preferred because it incurs no adverse endometrial effects and a progestogen is not required for endometrial protection [Rees and Purdie, 2006a]. Vaginal oestrogen therapy may be required long-term, as symptoms recur when treatment is stopped. However the endometrial safety of long term or repeated use of topical vaginal oestrogens is uncertain [CSM, 2003b].
  • Continuous combined hormone replacement therapy (HRT):
    • Cyclical HRT preparations may be used in postmenopausal women; however, continuous combined preparations are generally preferred because they do not induce bleeding.
    • Treatment for vasomotor symptoms should be continued for at least 1 year; otherwise, symptoms recur. Menopausal symptoms usually resolve within 2–5 years, but some women experience symptoms for many years, even into their seventies and eighties [Rees and Purdie, 2006a].
  • Tibolone:
    • There is evidence that tibolone is effective for treating vasomotor symptoms and improving sexual functioning.
  • Hot flushes and night sweats:
    • Good evidence indicates that systemic (oral and transdermal) HRT with oestrogen alone or oestrogens combined with progestogens is highly effective for reducing the frequency and severity of hot flushes and night sweats caused by the menopause.
  • Vaginal atrophy (dryness and dyspareunia):
    • There is evidence that HRT (combined oral oestrogens and progestogens or intravaginal oestrogens) is effective for treating symptoms of vaginal atrophy (dryness, burning and itching, and dyspareunia).
  • Sleep disturbances:
    • By alleviating night sweats, HRT often improves sleep. Women often report an improvement in sleep patterns with HRT even if hot flushes or night sweats are not prominent menopausal symptoms [ICSI, 2006]. There is evidence that combined oral oestrogen and progestogen therapy provides a small statistical but not clinically meaningful improvement in sleep disturbances.
  • Mood disturbances:
    • No evidence indicates that HRT has a direct effect on mood, irritability, or anxiety. However HRT may be helpful if other menopausal symptoms, such as hot flushes and sleep disturbances, are present [ICSI, 2006].
  • Libido:
    • HRT improves urogenital atrophy, thinning, dryness, and loss of elasticity, all of which may cause dyspareunia. While this may improve sexual functioning for many women, HRT has no proven direct benefit on sexuality or libido [ICSI, 2006].
    • There is evidence that loss of libido can be improved by testosterone supplementation, particularly after surgical menopause. Treatment is not always successful, other factors such as marital problems may be involved, and testosterone may cause potentially serious adverse effects [Rees and Purdie, 2006a].
    • Testosterone patches are licensed for women with surgically induced menopause (in women receiving concomitant oestrogen therapy), but they are not recommended for women naturally menopausal or those taking conjugated oestrogens. Safety and efficacy of testosterone patches have not been established beyond 1 year of treatment [BNF 54, 2007].
  • Recurrent urinary tract infections:
    • There is evidence that oral and intravaginal oestrogen is effective for preventing urinary tract infections. The appropriate dose and duration of therapy have not been established, and long-term treatment is required because symptoms recur when treatment is stopped [Rees and Purdie, 2006a].
  • Incontinence:
    • The British Menopause Society currently recommend the use of oral or topical oestrogen for urinary frequency and urgency [BMS, 2006a]. The evidence to support the use of oestrogens is conflicting. A Cochrane systematic review found evidence that oestrogen treatment improved or cured incontinence; this was more likely with urge incontinence [Moehrer et al, 2003]. However, a subsequently published analysis of the Women's Health Initiative trial found that oestrogen alone or combined with progestogen increased the risk of urinary incontinence among continent women and worsened urinary incontinence among symptomatic women after 1 year [Hendrix et al, 2005].

What follow up is required?

  • Review the woman 3 months after starting hormone replacement therapy (HRT) and once each year thereafter.
  • At the initial 3-month review:
    • Assess the effectiveness of treatment and adjust to achieve symptom control.
    • Enquire about any adverse effects and manage appropriately.
    • Enquire about bleeding patterns.
    • Check blood pressure and body weight.
  • Once each year:
    • Check effectiveness of treatment and adjust to achieve symptom control.
    • Check for adverse effects and manage appropriately.
    • Consider switching from cyclical HRT to continuous combined HRT, if appropriate.
    • Interrupt treatment with intravaginal oestrogen and consider stopping systemic HRT, to re-assess the need for continued use.
    • Explain that some of the risks (e.g. breast cancer, ovarian cancer) associated with HRT increase with longer duration of hormone replacement therapy (HRT):
      • Breast cancer: combined HRT increases this risk by about 1.6 times after 5 years of use and 2.3 times after 10 years of use. Risk decreases within a few years of stopping HRT.
      • Ovarian cancer: long-term use of oestrogen-only HRT and combined HRT may slightly increase the risk. Risk decreases after stopping HRT.
    • Perform a breast examination if indicated by personal or family history.
    • Encourage breast awareness and participation in the national breast screening programme as appropriate for their age.
    • Pelvic examination is required only if clinically indicated (e.g. if there is unscheduled bleeding, especially if heavy, prolonged, or recurrent).
    • Check blood pressure.
  • Oestrogen levels are rarely indicated.
Clarification / Additional information
  • Measurement of estradiol is rarely indicated but may be of use if the clinical response (i.e. symptomatic relief) to HRT is poor [Smellie et al, 2006]:
    • To establish whether absorption of transdermal HRT is adequate in women in whom poor absorption is suspected. If poor absorption is confirmed, prescribe oral HRT.
    • To ensure that oestrogen levels have fallen before implant replacement in women, to avoid supraphysiological concentrations and possible tachyphylaxis.
    • Rarely, in women with persisting symptoms where poor compliance is suspected.
Basis for recommendation
  • These recommendations are based on published expert opinion [Working Group on Breast and Pelvic Examination, 2001; RCPE, 2003; AACE Menopause Guidelines Revision Task Force, 2006; Rees and Purdie, 2006a; MHRA and CHM, 2007b; Roberts, 2007].
  • An initial review is recommended at 3 months, as most menopausal symptoms respond by then:
    • Vasomotor symptoms: improvement is usually noted within 4 weeks. Usually, hormone replacement therapy (HRT) is used for less than 5 years [BMS, 2006a].
    • Urogenital symptoms: topical oestrogens should be used in the lowest effective amount to minimize systemic absorption [CSM, 2003b]. However long term treatment is often required as symptoms can recur on cessation of therapy [BMS, 2006a]. Treatment should be interrupted as least annually to re-assess the need for continued treatment. If breakthrough bleeding or spotting appears at any time on therapy, the reason should be investigated and may include endometrial biopsy to exclude endometrial malignancy [CSM, 2003b].
  • An annual review is recommended because the risks and benefits of HRT for each woman change over time and need to be discussed regularly.
  • Blood pressure measurement is not routinely needed, but opportunistic screening is useful.
  • Measurement of follicle-stimulating hormone:
  • Measurement of oestrogen:
    • This recommendations is based on Best Practice in primary care pathology [Smellie et al, 2006].

When should I refer women who have started HRT?

  • Refer if:
    • Breakthrough bleeding persists for more than 4–6 months after starting HRT or tibolone.
    • A bleed occurs after amenorrhoea.
    • There is multiple treatment failure e.g. three or more regimens have been tried.
  • Refer to a team specializing in the management of gynaecological cancer (depending on local arrangements) any persistent or unexplained bleeding after cessation of hormone therapy for 6 weeks.
Basis for recommendation
  • This recommendation is based on pragmatic advice and published expert opinion [Rees and Purdie, 2006b].
  • Irregular bleeding or spotting can occur during the first 4–6 months of continuous combined therapy and tibolone and does not require investigation.

How should I manage women who have had a hysterectomy with HRT?

How should I manage women who have had a hysterectomy with HRT?

  • Offer lifestyle advice.
  • Advise the woman about the risks and benefits of oestrogen-based hormone replacement therapy (HRT) and record this in her notes.
  • Urogenital symptoms alone (e.g. vaginal dryness, dyspareunia, recurrent urinary tract infections, or urinary frequency and urgency):
    • Offer treatment with low-dose vaginal oestrogen (cream, pessary, tablet, or ring) or systemic (oral or transdermal) oestrogen replacement therapy:
      • Low-dose vaginal oestrogen may be preferred if the woman does not wish to take or cannot tolerate systemic oestrogen.
  • Vasomotor symptoms (e.g. hot flushes, night sweats), with or without urogenital symptoms:
    • Offer systemic (oral or transdermal), unopposed oestrogen replacement therapy.
  • Decreased libido:
    • Seek specialist advice if considering testosterone patches or implants.
  • For a full discussion on the choice of HRT preparations, see Type of product to offer.
Clarification / Additional information
  • Urogenital symptoms: long term treatment is often required as symptoms can recur on cessation of therapy.
  • Vasomotor symptoms generally respond to systemic therapy within 4 weeks of starting treatment and have a maximal therapeutic effect at 3 months.
Basis for recommendation
  • These recommendations are based on published expert opinion and evidence from systematic reviews and large randomized controlled trials [NZGG, 2004; ICSI, 2006; Rees and Purdie, 2006a; MHRA and CHM, 2007b].
  • Oestrogen therapy:
    • Hysterectomized women should be given oestrogen alone and have no need for progestogen therapy [Rees and Purdie, 2006a]. Progestogens are added to oestrogen therapy to reduce the risk of endometrial hyperplasia and carcinoma which occurs with unopposed oestrogen.
    • Treatment for vasomotor symptoms should be continued for at least 1 year; otherwise, symptoms recur. Menopausal symptoms usually resolve within 2–5 years, but some women experience symptoms for many years, even into their seventies and eighties [Rees and Purdie, 2006a].
  • Libido:
    • Hormone replacement therapy (HRT) improves urogenital atrophy, thinning, dryness, and loss of elasticity, all of which may cause dyspareunia. While this may improve sexual functioning for many women, HRT has no proven direct benefit on sexuality or libido [ICSI, 2006].
    • There is evidence that loss of libido can be improved by testosterone supplementation, particularly after surgical menopause. Specialist advice should be sought because it is not successful in all women and other factors such as marital problems may be involved [Rees and Purdie, 2006a].
    • Testosterone patches are licensed for women with surgically induced menopause (in women receiving concomitant oestrogen therapy), but they are not recommended for women naturally menopausal or those taking conjugated oestrogens. Safety and efficacy of testosterone patches have not been established beyond 1 year of treatment [BNF 54, 2007].
  • Hot flushes and night sweats:
    • Good evidence indicates that systemic HRT with oestrogen alone or oestrogens combined with progestogens is highly effective for reducing the frequency and severity of hot flushes and night sweats caused by the menopause.
  • Vaginal atrophy (dryness and dyspareunia):
    • There is evidence that HRT (combined oral oestrogens and progestogens or intravaginal oestrogens) is effective for treating vaginal atrophy (dryness, burning and itching, and dyspareunia).
  • Recurrent urinary tract infections:
    • There is evidence that oral or intravaginal oestrogen is effective for preventing urinary tract infections. The appropriate dose and duration of therapy have not been established, and long-term treatment is required because symptoms recur when treatment is stopped [Rees and Purdie, 2006a].
  • Sleep disturbances:
    • By alleviating night sweats, HRT often improves sleep. Women often report an improvement in sleep patterns with HRT even if hot flushes or night sweats are not prominent menopausal symptoms [ICSI, 2006]. There is evidence that combined oral oestrogen and progestogen therapy provides a small statistical but not clinically meaningful improvement in sleep disturbances.
  • Incontinence:
    • The British Menopause Society currently recommend the use of oral or topical oestrogen for urinary frequency and urgency [BMS, 2006a]. The evidence to support the use of oestrogens is conflicting. A Cochrane systematic review found evidence that oestrogen treatment improved or cured incontinence; this was more likely with urge incontinence [Moehrer et al, 2003]. However, a subsequently published analysis of the Women's Health Initiative trial found that oestrogen therapy alone and combined with progestogen therapy increased the risk of urinary incontinence among continent women and worsened urinary incontinence among symptomatic women after 1 year [Hendrix et al, 2005].
  • Mood disturbances:
    • No evidence indicates that HRT has a direct effect on mood, irritability, or anxiety. However, HRT may be helpful if other menopausal symptoms, such as hot flushes and sleep disturbances, are present [ICSI, 2006].

Are there any specific issues I should consider in a woman who has had a subtotal hysterectomy?

  • A remnant of endometrial tissue may be present in women who have had a subtotal hysterectomy (in which the main part of the uterus is removed but the cervix is retained).
  • To test for the presence of endometrial tissue, prescribe a 3-month course of cyclical hormone replacement therapy (HRT):
    • If withdrawal bleeding occurs, endometrial tissue is present, and combined HRT should be started:
    • If the woman does not have withdrawal bleeding, endometrial tissue is unlikely to be present, and oestrogen-only HRT may be started:
Basis for recommendation

What follow up is required?

  • Review 3 months after starting hormone replacement therapy (HRT) and once each year thereafter.
  • At the initial 3-month review:
    • Assess the effectiveness of treatment and adjust to achieve symptom control.
    • Enquire about any adverse effects and manage appropriately.
    • Check blood pressure and body weight.
  • Once each year:
    • Check effectiveness of treatment and adjust to achieve symptoms control.
    • Check for adverse effects and manage appropriately.
    • Re-assess the need for continuing HRT.
    • Explain that some of the risks (e.g. ovarian cancer) associated with oestrogen-only HRT increase with longer duration of HRT. The risk decreases after stopping HRT.
    • Perform a breast examination if indicated by personal or family history.
    • Encourage breast awareness and participation in the national breast screening programme as appropriate for their age.
    • Check blood pressure.
  • Oestrogen levels are rarely indicated.
Clarification / Additional information
  • Measurement of estradiol is rarely indicated but may be of use if the clinical response (i.e. symptomatic relief) to transdermal HRT is poor [Smellie et al, 2006]:
    • To establish whether absorption of transdermal HRT is adequate. If poor absorption is confirmed, prescribe oral HRT.
    • To ensure that oestrogen levels have fallen before implant replacement in women, to avoid supraphysiological concentrations and possible tachyphylaxis.
    • Rarely, in women with persisting symptoms where poor compliance is suspected.
Basis for recommendation
  • These recommendations are based on published expert opinion [Working Group on Breast and Pelvic Examination, 2001; RCPE, 2003; AACE Menopause Guidelines Revision Task Force, 2006; Rees and Purdie, 2006a; MHRA and CHM, 2007b; Roberts, 2007].
  • Review at 3 months:
    • An initial review is recommended at 3 months, as most menopausal symptoms respond by then:
      • Vasomotor symptoms: improvement is usually noted within 4 weeks. Usually, hormone replacement therapy (HRT) is used for less than 5 years [BMS, 2006a].
      • Urogenital symptoms: vaginal dryness, soreness, superficial dyspareunia, and urinary frequency and urgency respond well to topical or systemic oestrogens. Improvement may take several months, and symptoms may recur if treatment is stopped. Long-term treatment is often required [BMS, 2006a].
  • Annual review:
    • An annual review is recommended because the risks and benefits of HRT for each woman change over time and need to be discussed regularly.
    • Blood pressure measurement is not routinely needed, but opportunistic screening is useful.
  • Measurement of follicle-stimulating hormone:
  • Measurement of oestrogen:
    • This recommendations is based on Best Practice in primary care pathology [Smellie et al, 2006].

When should I refer women who have started HRT?

  • Refer to secondary care if there is multiple treatment failure e.g. three or more regimens have been tried.
Basis for recommendation

What should I do if there is poor symptom control?

  • Review the woman:
    • Check that the hormone replacement therapy (HRT) has been used as recommended for at least 3 months to ensure full effect.
    • Check that patches are adherent.
    • Review the woman's expectations. Hormone replacement therapy can help symptoms due to oestrogen deficiency but is not an answer to all problems.
    • Consider an alternative diagnosis. See Other causes of the symptoms.
  • Treatment options include:
    • Increasing the oestrogen dose.
    • Adding vaginal oestrogen if urogenital symptoms are not controlled.
    • Switching from oral to a non-oral route (e.g. if absorption is poor because of a bowel disorder or if a drug interaction is present).
    • Switching delivery system if patch adhesion is poor.
Basis for recommendation

When should I consider stopping HRT?

  • If systemic HRT is being used for symptom control consider a trial withdrawal (if a woman is symptom-free) after 1–2 years of hormone replacement therapy (HRT).
    • Advise the woman that symptoms may recur for a short time once HRT is stopped.
    • Counsel the woman about the possible risks of HRT if she wishes to continue treatment, particularly if treatment is being used for longer than 5 years.
  • Topical (vaginal) oestrogen may be required long term as symptoms can recur once treatment has stopped.
    • Stop treatment at least annually to re-assess the need for continued treatment.
  • Women with premature menopause usually take hormone replacement therapy up to the age of the natural menopause (50 years); at that time, therapy is reassessed. Some women will still be symptomatic.
Basis for recommendation
  • These recommendations are based on pragmatic advice and published expert opinion [RCPE, 2003; Rees and Purdie, 2006a].
  • Vasomotor symptoms usually resolve within 2–5 years, but some women experience symptoms for many years.
  • Topical oestrogens:
    • Endometrial effects should not be incurred with low dose oestrogens such as vaginal estriol (cream or pessary) or estradiol (tablet or ring). A progestogen is not needed with such low dose preparations [Rees and Purdie, 2006a].
    • The endometrial safety of long-term or repeated use of topical vaginal oestrogens is uncertain. The Medicines and Healthcare products Regulatory Agency (MHRA) have advised that treatment with topical oestrogens should be interrupted at least annually to re-assess the need for continued treatment [CSM, 2003b].

How should I manage women with a premature menopause?

How can I manage women with a premature menopause?

  • Offer lifestyle advice.
  • Refer women who are younger than 40 years of age to a gynaecologist.
  • Offer systemic oestrogen replacement therapy.
    • Systemic hormone replacement therapy (HRT) or the combined oral contraceptive pill (COC) may be used.
  • HRT: the HRT regimens used will depend on whether or not the woman has undergone a hysterectomy, still has some ovarian activity, and still has periods.
    • For women who are still having periods, offer combined, systemic (oral or transdermal), cyclical HRT:
      • For women with infrequent periods or who cannot tolerate progestogens, a systemic 3-monthly regimen may be preferred.
    • For women who have had a hysterectomy, offer oral or transdermal unopposed oestrogen replacement therapy.
  • COC: whether or not the woman can be prescribed the COC will depend upon the woman's age and associated risk factors (e.g. smoking).
  • Advise the woman that she may still become pregnant if contraception is not used.
    • See the CKS topic on Contraception for a detailed discussion on the use of contraception in perimenopausal women.
  • Testosterone implants and patches (licensed) may be considered for treating decreased libido (especially in oophorectomized women); however, seek specialist advice before prescribing.
Clarification / Additional information
  • For the purposes of this guideline, premature menopause is menopause which occurs in women less than 45 years of age.
  • After 50 years of age, therapy for osteoporosis should be reassessed.
Basis for recommendation
  • These recommendations are based on published expert opinion [CSM, 2003a; Rees and Purdie, 2006a; SOGC, 2006].
  • Feedback from expert reviewers recommend that women less than 40 years of age should be referred for investigation to determine the cause of premature menopause (e.g. primary ovarian failure) and to discuss fertility if appropriate. Women who have primary ovarian failure may continue to ovulate infrequently and require advice on appropriate contraception.
  • Hormone replacement therapy (HRT):
  • The combined oral contraceptive (COC) containing oestrogen and progestogen:
    • The COC is often prescribed for younger women because it does not have the stigma of old age that HRT may have. However, trial evidence is scant on which to recommend treatment with a COC [Rees and Purdie, 2006a; SOGC, 2006]. The COC is perhaps more useful when contraception is still thought to be required (e.g. ovulation can occur for several years after premature ovarian failure in some women).
    • The dose of ethinylestradiol used in standard pills is sufficient to provide control of menopausal symptoms and osteoporosis prophylaxis; however, oral contraceptives provide oestrogen for only 3 weeks in every 4 (the fourth week being pill-free). For women who are oestrogen deficient, the lack of oestrogen during this pill-free week can cause symptoms, and it may be more appropriate to provide oestrogen continuously, as with most forms of HRT.
  • Testosterone:
    • There is evidence that loss of libido can be improved by testosterone supplementation particularly after surgical menopause. Treatment is not always successful, other factors such as marital problems may be involved, and and testosterone may cause potentially serious adverse effects [Rees and Purdie, 2006a].

What follow-up is required?

  • Review 3 months after starting hormone replacement therapy (HRT) and once each year thereafter.
  • At the initial 3-month review:
    • Assess the effectiveness of treatment and adjust to achieve symptom control.
    • Enquire about any adverse effects and manage appropriately.
    • Check blood pressure and body weight.
  • Once each year:
    • Check effectiveness of treatment and adjust to achieve symptoms control.
    • Check for adverse effects and manage appropriately.
    • Interrupt treatment with intravaginal oestrogen to re-assess the need for continued use.
    • Re-assess the need for continuing systemic HRT.
    • Explain that some of the risks (e.g. ovarian cancer) associated with oestrogen-only HRT increase with longer duration of HRT. The risk decreases after stopping HRT.
    • Perform a breast examination if indicated by personal or family history.
    • Encourage breast awareness and participation in the national breast screening programme as appropriate for their age.
    • Pelvic examination is required only if clinically indicated (e.g. if there is unscheduled bleeding, especially if heavy, prolonged, or recurrent).
    • Check blood pressure.
  • Oestrogen levels are rarely indicated.
Clarification / Additional information
  • Measurement of estradiol is rarely indicated but may be of use if the clinical response (i.e. symptomatic relief) to transdermal HRT is poor [Smellie et al, 2006]:
    • To establish whether absorption of transdermal HRT is adequate. If poor absorption is confirmed, prescribe oral HRT.
    • To ensure that oestrogen levels have fallen before implant replacement in women, to avoid supraphysiological concentrations and possible tachyphylaxis.
    • Rarely, in women with persisting symptoms where poor compliance is suspected.
Basis for recommendation
  • These recommendations are based on published expert opinion [Working Group on Breast and Pelvic Examination, 2001; RCPE, 2003; AACE Menopause Guidelines Revision Task Force, 2006; Rees and Purdie, 2006a; MHRA and CHM, 2007b; Roberts, 2007].
  • Review at 3 months:
    • An initial review is recommended at 3 months, as most menopausal symptoms respond by then:
      • Vasomotor symptoms: improvement is usually noted within 4 weeks. Usually, hormone replacement therapy (HRT) is used for less than 5 years [BMS, 2006a].
      • Urogenital symptoms: vaginal dryness, soreness, superficial dyspareunia, and urinary frequency and urgency respond well to topical or systemic oestrogens. Improvement may take several months, and symptoms may recur if treatment is stopped. Long-term treatment is often required [BMS, 2006a].
  • Annual review:
    • An annual review is recommended because the risks and benefits of HRT for each woman change over time and need to be discussed regularly.
    • Blood pressure measurement is not routinely needed, but opportunistic screening is useful.
  • Measurement of follicle-stimulating hormone:
  • Measurement of oestrogen:
    • This recommendations is based on Best Practice in primary care pathology [Smellie et al, 2006].

When should I refer a women with premature menopause who has started HRT?

  • For women taking cyclical hormone replacement therapy refer if:
    • There is a change in pattern of withdrawal bleeds or breakthrough bleeding.
  • For women taking continuous combined HRT or long cycle regimens refer if:
    • Breakthrough bleeding persists for more than 4–6 months after starting therapy.
    • A bleed occurs after amenorrhoea.
  • Refer if there is multiple treatment failure e.g. three or more regimens have been tried.
  • Refer to a team specializing in the management of gynaecological cancer (depending on local arrangements) any persistent or unexplained bleeding after cessation of hormone therapy for 6 weeks.
Basis for recommendation

How can I manage menopausal symptoms without HRT?

How can I manage menopausal symptoms without HRT?

  • Offer lifestyle advice to control symptoms; if this is not effective, consider other treatments.
  • For vasomotor symptoms, consider:
    • A trial (2 weeks) of paroxetine (20 mg daily), fluoxetine (20 mg daily), citalopram (20 mg daily), or venlafaxine 37.5 mg twice a day.
      • Antidepressants are unlicensed for treating menopausal symptoms.
    • A trial (2–4 weeks) of clonidine (50 to 75 micrograms twice a day, licensed use).
    • Seek specialist advice if a progestogen such as norethisterone or megestrol (both unlicensed) are being considered.
  • For vaginal dryness, prescribe a vaginal lubricant or moisturizer, such as Replens MD®.
  • Manage psychological symptoms, such as mood disturbances, anxiety, and depression, on an individual basis. They may be addressed using self-help groups, psychotherapy, other forms of counselling, or antidepressants.
  • CKS does not recommend the use of complementary therapies (e.g. soy, red clover, black cohosh). If complementary or herbal products are being used, advise the woman that:
    • The efficacy of these products has not yet been established.
    • There is very little control over the quality of the products available, which may vary considerably.
    • Some of these treatments (ginseng, black cohosh, and red clover) have oestrogenic properties and should not be used in women with contraindications to oestrogen (e.g. breast cancer).
    • Long-term safety (e.g. effects on the breast and endometrium) have not been assessed.
    • Some treatments may have serious adverse effects (e.g. liver toxicity has been reported with black cohosh and kava):
      • Kava has been withdrawn from the UK market.
    • Dong quai extracts and some species of red clover contain coumarins, which make them unsuitable for women taking anticoagulants.
Basis for recommendation
  • These recommendations are based on published expert opinion from the Medicines and Healthcare products Regulatory Agency, formerly known as the Committee on Safety of Medicines [CSM, 2003; CSM, 2004; ICSI, 2006; RCOG, 2006; Rees and Purdie, 2006].
  • Progestogens:
    • There is evidence that norethisterone and megestrol are effective for treating hot flushes. However, doses which achieve vasomotor control may increase the risk of thromboembolism and may not be suitable for women at increased risk of thromboembolic disease (personal or family history, known thrombophilia) [BMS, 2006]. Long term safety data is lacking.
  • Antidepressants:
    • Limited evidence indicates that venlafaxine, fluoxetine, citalopram, and paroxetine are effective for treating hot flushes. They are not licensed for this use but may be considered in treating women who cannot, or do not want to take hormone replacement therapy.
    • When effective, antidepressants provide relief from hot flushes almost immediately. A 1-week trial is generally sufficient to determine whether an antidepressant is going to be effective [ICSI, 2006].
  • Clonidine:
    • Clonidine is licensed for the treatment of vasomotor symptoms. There is limited evidence of its efficacy. It may cause unacceptable adverse effects (e.g. dry mouth, sedation, depression, fluid retention) [Rees and Purdie, 2006; BNF 54, 2007].
    • Clonidine should be stopped if no benefit is noted after 2–4 weeks of treatment or if a woman experiences adverse effects, including dizziness, dry mouth, drowsiness, and constipation [SOGC, 2006].
  • Complementary therapies:
    • No convincing evidence indicates that complementary therapies are effective for managing menopausal symptoms, but prospective randomized controlled trials are required to confirm the efficacy and long-term safety of these therapies [RCOG, 2006].
  • Other treatments:
    • Gabapentin:
      • Limited evidence indicates that gabapentin is effective for reducing hot flushes; further work is being done to confirm this, and use of gabapentin is restricted to specialist centres [RCOG, 2006].
    • Beta-blockers:

What follow up is required?

  • Advise the woman to return if:
    • Lifestyle measures alone have been of insufficient benefit or her symptoms worsen.
    • She does not respond to antidepressant treatment within 2 weeks.
    • Clonidine was started and her symptoms have not improved in 4 weeks, or she is experiencing adverse effects, such as dizziness or constipation.
  • Review all women at least annually.
Basis for recommendation
  • There is no published guidance on when to follow up menopausal women who are being treated with alternatives to hormone replacement therapy. These recommendations are based on pragmatic advice.
  • Women who are going to respond to antidepressants generally do so within 1–2 weeks.
  • Women who start clonidine therapy usually respond to treatment within 2–4 weeks.

When should I consider stopping treatment?

  • Consider stopping treatment if a woman is symptom-free on treatment; a trial withdrawal can be undertaken after 1–2 years of therapy.
  • Advise that symptoms sometimes recur once treatment is stopped.
  • Use of vaginal moisturizers and lubricants may be continued indefinitely.
Basis for recommendation
  • There is no published guidance on the duration of therapy for alternatives to hormone replacement therapy.
  • Vasomotor symptoms usually resolve within 2–5 years [Rees and Purdie, 2006a].

How should I manage women with a comorbidity?

How should I manage a woman with current or previous endometrial cancer?

  • Offer lifestyle advice or non-HRT therapies initially.
  • If these are inadequate and the woman requires treatment, seek specialist advice from an oncologist or a specialist menopause clinic for the most appropriate treatment.
Clarification / Additional information
  • Management usually depends on the stage of the cancer. Treatment with hormone replacement therapy is usually limited to women with stage I disease, although women with stage II disease are occasionally treated.
  • In stage I endometrial cancer, specialists may advise that oestrogens can sometimes be used. Progestogens (in opposition to oestrogen or alone) may also be used.
Basis for recommendation

How should I manage a woman with a personal or family history of thromboembolic disease or with a known thrombophilia disorder?

Basis for recommendation
  • These recommendations are based on published expert opinion [RCOG, 2004; ICSI, 2006].
  • Women with a personal or family history of thromboembolic disease should avoid using oral hormone replacement therapy (HRT) (in view of the relatively high risk of recurrent venous thromboembolism [VTE]) unless it is taken with anticoagulation therapy:
    • Transdermal therapy may be a better option, but specialist advice should be sought.
    • Evidence indicates that oral HRT and not transdermal HRT is associated with an increased risk of VTE.
    • Transdermal therapy is thought to have less effect on coagulation than oral administration because oral preparations undergo first-pass hepatic metabolism and therefore have a greater effect on factors produced by the liver than transdermal preparations, which avoid the first-pass effect.
  • Women with a known thrombophilia disorder:
    • In general, women with antithrombin defects, or combinations of other clotting defects, and Factor V Leiden homozygosity should avoid HRT, unless it is taken with anticoagulation therapy (these women should be managed via specialist centres).
    • Evidence is insufficient to recommend that women with other clotting defects completely avoid HRT. However, HRT should be avoided in the presence of multiple risk factors for VTE in these women (e.g. varicose veins, obesity).

How should I manage a woman with current or previous breast cancer?

  • Offer lifestyle advice or non-HRT therapies initially.
  • If a woman with a significant family history of breast cancer requires hormone replacement therapy (HRT), refer to a specialist breast clinic to determine her personal risk, without which an informed decision cannot be made.
  • For women with current or previous breast cancer who have severe menopausal symptoms, seek specialist advice from the local oncologist or specialist menopausal clinic.
Basis for recommendation
  • This recommendation is based on published expert opinion [Rees and Purdie, 2006a].
  • Hormone replacement therapy remains contraindicated in women who have had breast cancer.
  • Troublesome symptoms of oestrogen deficiency are common in women receiving treatment for breast cancer. Hormone replacement therapy has been given with tamoxifen but should be avoided in women taking aromatase inhibitors (e.g. anastrozole) [RCPE, 2003].

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