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].

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

There is evidence that HRT reduces the risk of both spine and hip as well as other osteoporotic fractures. A few years treatment with HRT around the time of menopause may have a long term effect on fracture reduction [Writing Group for the Women's Health Initiative Investigators, 2002; Women's Health Initiative, 2004].

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].

Other benefits

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.

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].

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.

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].

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].

Initial and annual review

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

Follicle-stimulating hormone should not be measured because it does not reflect the adequacy of the oestrogen dose and levels may remain increased despite an adequate oestrogen effect [AACE Menopause Guidelines Revision Task Force, 2006].

Measurement of oestrogen

This recommendations is based on Best Practice in primary care pathology [Smellie et al, 2006].

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.

These recommendations are based on published expert opinion [Rees and Purdie, 2006a].

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].

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

There is evidence that HRT reduces the risk of both spine and hip as well as other osteoporotic fractures. A few years treatment with HRT around the time of menopause may have a long term effect on fracture reduction [Writing Group for the Women's Health Initiative Investigators, 2002; Women's Health Initiative, 2004].

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].

Other benefits

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.

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].

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.

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.

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.

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].

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].

Initial and annual review

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

Follicle-stimulating hormone should not be measured because it does not reflect the adequacy of the oestrogen dose and levels may remain increased despite an adequate oestrogen effect [AACE Menopause Guidelines Revision Task Force, 2006].

Measurement of oestrogen

This recommendations is based on Best Practice in primary care pathology [Smellie et al, 2006].

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.

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].

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

There is evidence that HRT reduces the risk of both spine and hip as well as other osteoporotic fractures. A few years treatment with HRT around the time of menopause may have a long term effect on fracture reduction [Writing Group for the Women's Health Initiative Investigators, 2002; Women's Health Initiative, 2004].

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].

Other benefits

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.

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].

These recommendations are based on published expert opinion [Rees and Purdie, 2006a].

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].

Initial and annual review

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

Follicle-stimulating hormone should not be measured because it does not reflect the adequacy of the oestrogen dose and levels may remain increased despite an adequate oestrogen effect [AACE Menopause Guidelines Revision Task Force, 2006].

Measurement of oestrogen

This recommendations is based on Best Practice in primary care pathology [Smellie et al, 2006].

This recommendation is based on pragmatic advice and published expert opinion [Rees and Purdie, 2006b].

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].

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

There is evidence that HRT reduces the risk of both spine and hip as well as other osteoporotic fractures. A few years treatment with HRT around the time of menopause may have a long term effect on fracture reduction [Writing Group for the Women's Health Initiative Investigators, 2002; Women's Health Initiative, 2004].

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].

Other benefits

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.

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].

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.

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)

Women who have premature menopause require treatment to prevent osteoporosis and to treat menopausal symptoms. There is evidence that HRT reduces the risk of spine and hip fracture, as well as other osteoporotic fractures [Writing Group for the Women's Health Initiative Investigators, 2002; Women's Health Initiative, 2004].

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].

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

Follicle-stimulating hormone should not be measured because it does not reflect the adequacy of the oestrogen dose and levels may remain increased despite an adequate oestrogen effect [AACE Menopause Guidelines Revision Task Force, 2006].

Measurement of oestrogen

This recommendations is based on Best Practice in primary care pathology [Smellie et al, 2006].

This recommendation is based on pragmatic advice and published expert opinion [Rees and Purdie, 2006b].