Menopausal symptoms

Prescribing Notes:

• The MHRA advises that before prescribing hormone-replacement therapy, healthcare professionals should consider carefully the potential benefits and risks for every woman.

Short-term treatment of menopausal symptoms

• HRT can be prescribed for troublesome menopausal symptoms which affect quality of life and wellbeing. Women should be helped to make an informed choice about taking HRT or not.
• Women with premature ovarian insufficiency (early menopause) should consider use of HRT up to the age of normal menopause, i.e. 50 years, with at least 50micrograms of estrogen transdermally or equivalent to prevent osteoporosis.
• It is recommended that the lowest dose of HRT based on relieving menopausal symptoms should be prescribed.
• Patients should be started on low dose preparations and the dose increased if there is inadequate symptom control.
• Patient preference is important for adherence, therefore a range of suitable products are suggested.
• Tablets avoid problems with detachment from skin and local side-effects.
• Transdermal HRT has less risk of venous thromboembolism and should be used preferentially in women who are older, who have cardiovascular risk factors or women with risk factors for VTE (including women with BMI>30). Transdermal regimens should be considered in women intolerant of or unable to take oral HRT, or in those with migraines, epilepsy and some gastro-intestinal conditions. Patches may be appropriate in patients in whom there is a clinical need to avoid first pass metabolism of oestrogens (e.g. patients with liver disease, or diabetes), or express a strong preference for patches. 
• Women should be reviewed three months after commencing HRT. Blood pressure should be checked 6-12 monthly, and women encouraged to participate in screening programmes for cervical cytology and mammography. Breast awareness should be encouraged but routine examination or extra mammograms are not required. The ongoing need for HRT should be reassessed annually.
• HRT can be withdrawn either abruptly or using decreasing doses over 3-6 months to minimise the risk of menopausal symptoms returning. It is accepted practice that HRT matrix patches can be cut to facilitate dose reduction (although this is unlicensed).
• HRT is not a method of contraception. Perimenopausal women may need to continue or add in a method of contraception while taking HRT.
• Mirena is effective as the progestogen component of HRT in combination with an oestrogen-only preparation. Perimenopausal women who have an existing Mirena inserted for contraception and/or to treat heavy bleeding can add oestrogen if HRT is required and the Mirena is in date.
• HRT is usually contra-indicated in the presence of active venous thromboembolism, unexplained vaginal bleeding, oestrogen dependent tumours (breast, endometrial and some ovarian cancers), current or recent cardiovascular disease and acute porphyria. Women with severe menopausal symptoms following some of these conditions may occasionally be prescribed HRT after specialist consultation.
• Medical alternatives to HRT for treatment of severe menopausal symptoms are limited but low dose antidepressant drugs may improve mood, sleep and reduce vasomotor symptoms, such as SSRIs. The use of antidepressants for treating menopausal symptoms is off-label. Other medical alternatives can include gabapentin, pregabalin and oxybutynin.
• Lifestyle changes should always be recommended to improve wellbeing of women with menopausal symptoms. CBT techniques, weight loss, healthy diet, mindfulness can all improve quality of life at this time.

HRT and cardiovascular disease

• There is no evidence that HRT protects against either ischaemic heart disease or stroke and it should not be started for this indication. HRT may be associated with worsening of cardiovascular outcome, particularly in older women with pre-existing cardiovascular risk factors. If a woman develops an acute CVD event, e.g. heart attack or stroke, or is immobilised while receiving HRT, the risk of thromboembolism is increased and consideration should be given to stopping HRT. Transdermal HRT is safer in respect of thrombosis so should be prescribed rather than oral HRT.

HRT and breast cancer

• New data summarised by the MHRA confirmed that the risk of breast cancer is increased during use of all types of HRT, except vaginal oestrogens, and increases with increasing duration of HRT use and that an excess risk of breast cancer persists for longer after stopping HRT than previously thought.
• All types of systemic HRT are associated with an increased risk of breast cancer, but the risk is higher for combined oestrogen-progestogen HRT than for oestrogen-only therapy.
• Only prescribe HRT for relief of menopause symptoms that adversely affect quality of life, and regularly review patients to ensure HRT is used for the shortest time at the lowest dose.
• Prescribers of HRT should discuss the updated total risk with women using HRT at their next routine appointment.
• Remind current and past HRT users to be vigilant for signs of breast cancer and encourage them to attend for breast screening when invited.
• Women with a significant family history should seek specialist opinion prior to being prescribed HRT.
• Tibolone also has an increased risk of breast cancer.
• The additional risk of breast cancer begins to decline when HRT is stopped but excess risk persists for more than 10 years after stopping HRT. The need for HRT should be reassessed at least annually.
• MHRA provides a summary table of risk of breast cancer associated with combined oestrogen-progestogen HRT and benefits, excluding menopausal symptom relief, during current use and current use plus post-treatment from age of menopause up to age 69 years, per 1000 women with 5 years or 10 years use of HRT.  See the full MHRA guidance here.

HRT and osteoporosis

• HRT prevents loss of bone density and reduces risk of osteoporotic fracture. In general, it should not be used as first-line for prevention of osteoporosis as the risk:benefit ratio of HRT is unfavourable but may still be recommended for women with premature ovarian insufficiency (early menopause). See Osteoporosis recommendations.

Prescribing Notes:

• The MHRA advises that before prescribing hormone-replacement therapy, healthcare professionals should consider carefully the potential benefits and risks for every woman.
• Women under 54 years of age or within 12 months of last menstrual period should receive cyclical HRT.
• There will be a regular bleed associated with sequential combined HRT.
• Switching between different types of progesterone may improve tolerability in some patients. Combined HRT regimens contain either: less androgenic progestogens medroxyprogesterone or dydrogesterone or a more androgenic progestogens norethisterone or levonorgestorel. Micronised progesterone is an alternative oral option in combination with transdermal oestrogen for patients who do not tolerate synthetic progestogens.
• Evidence suggests that micronised progesterone or dydrogesterone are unlikely to increase the risk of venous thrombosis and are associated with a lower risk of breast cancer compared to other progestogen preparations. For individuals at a higher risk of venous thrombosis or breast cancer, consider micronised progesterone or dydrogesterone in combination with estradiol.
• If standard estrogen doses do not provide adequate symptom control seek specialist advice. When high dose estrogen is required for symptom management, higher oral progestogen doses are suggested for adequate endometrial protection, refer to British Menopause Society resources for more information.
• Prolonged use of cyclical HRT can increase the risk of endometrial cancer. Women should not normally be kept on cyclical therapy for longer than 5 years. After 5 years they should be changed to a continuous combined regimen instead.

Prescribing Notes:

• The MHRA advises that before prescribing hormone-replacement therapy, healthcare professionals should consider carefully the potential benefits and risks for every woman.
• Switching between different types of progesterone may improve tolerability in some patients Combined HRT regimens contain either: less androgenic progestogen medroxyprogesterone or more androgenic progestogens norethisterone or levonorgestrel. Micronised progesterone is an alternative oral option in combination with transdermal oestrogen for patients who do not tolerate synthetic progestogens.
• Evidence suggests that micronised progesterone is unlikely to increase the risk of venous thrombosis and is associated with a lower risk of breast cancer compared to other progestogen preparations. For individuals at a higher risk of venous thrombosis or breast cancer, consider micronised progesterone in combination with estradiol.
• If standard estrogen doses do not provide adequate symptom control seek specialist advice. When high dose estrogen is required for symptom management, higher oral progestogen doses are suggested for adequate endometrial protection, refer to British Menopause Society resources for more information.
• Preparations containing 50micrograms estradiol (transdermal) are an appropriate choice for second line use in osteoporosis prophylaxis.

Prescribing Notes:

• The MHRA advises that before prescribing hormone-replacement therapy, healthcare professionals should consider carefully the potential benefits and risks for every woman.
• Continuous combined therapy (period-free HRT) should be used by women who are at least a year past the menopause or over 54 years of age. Both estrogen and progestogen are taken daily to give a period-free regimen. Erratic bleeding is common in the first few months of use.
• Women with irregular or heavy bleeding with HRT which persists for more than 3 months should be referred to a gynaecology or menopause service.
• Amenorrhoea with HRT is not a risk for endometrial cancer and does not require investigation.
• Continuous combined therapy is also used as ’add-back HRT’ for women on long-term gonadorelin analogues.
• Switching between different types of progesterone may improve tolerability in some patients. Combined HRT regimens contain either: less androgenic progestogens medroxyprogesterone or dydrogesterone or a more androgenic progestogen norethisterone.
• If standard estrogen doses do not provide adequate symptom control seek specialist advice. When high dose estrogen is required for symptom management, higher oral progestogen doses are suggested for adequate endometrial protection, refer to British Menopause Society resources for more information.
• The progestogen-only intrauterine device (Mirena IUS) may also be used to provide the progestogen part in women on HRT. If used under these circumstances, it is only licensed for 4 years of use, however FSRH guidance states it can be used safely for 5 years.
• Tibolone is a synthetic steroid compound with mixed oestrogenic, progestogenic and androgenic properties, and can be used for women with an intact uterus. It relieves menopausal vasomotor and urogenital symptoms. It has beneficial effects on libido, mood and bone loss.
• Tibolone is the preferred choice in women with a history of endometriosis and in women with reduced libido not resolved by conventional HRT or psychological intervention.
• Tibolone has a higher risk of venous thromboembolism than other types of HRT.
• Tibolone is not suitable for use in the pre-menopausal stage or within 12 months of the last menstrual period.

Prescribing Notes:

• The MHRA advises that before prescribing hormone-replacement therapy, healthcare professionals should consider carefully the potential benefits and risks for every woman.
• Continuous combined therapy (period-free HRT) should be used by women who are at least a year past the menopause or over 54 years of age. Both estrogen and progestogen are taken daily to give a period-free regimen. Erratic bleeding is common in the first few months of use.
• Women with irregular or heavy bleeding with HRT which persists for more than 3 months should be referred to a gynaecology or menopause service.
• Amenorrhoea with HRT is not a risk for endometrial cancer and does not require investigation.
• Continuous combined therapy is also used as ’add-back HRT’ for women on long-term gonadorelin analogues.
• Switching between different types of progesterone may improve tolerability in some patients. Combined HRT regimens contain either: a less androgenic progestogen medroxyprogesterone or more androgenic progestogens norethisterone or levonorgestrel. Micronised progesterone is an alternative oral option in combination with transdermal oestrogen for patients who do not tolerate synthetic progestogens.
• Evidence suggests that micronised progesterone is unlikely to increase the risk of venous thrombosis and is associated with a lower risk of breast cancer compared to other progestogen preparations. For individuals at a higher risk of venous thrombosis or breast cancer, consider micronised progesterone in combination with estradiol.
• If standard estrogen doses do not provide adequate symptom control seek specialist advice. When high dose estrogen is required for symptom management, higher oral progestogen doses are suggested for adequate endometrial protection, refer to British Menopause Society resources for more information.
• The progestogen-only intrauterine device (Mirena IUS) may also be used to provide the progestogen part in women on HRT. If used under these circumstances, it is only licensed for 4 years of use, however FSRH guidance states it can be used safely for 5 years.

Prescribing Notes:

• The MHRA advises that before prescribing hormone-replacement therapy, healthcare professionals should consider carefully the potential benefits and risks for every woman.
• Prescribe estradiol tablets generically; different brands of the same formulation are available.

Prescribing Notes:

• Patient criteria for testosterone:
  • Menopausal patients with secondary and generalised low sexual desire for at least six months
  • Symptoms severe enough to cause distress or negatively impact quality of life and/or interpersonal relationships
  • Persistence of symptoms, despite optimal oestrogenisation with systemic HRT (and where indicated, local vaginal oestrogen)
  • Other potential causes of low sexual desire considered and/or excluded e.g. sexual pain, psychosexual problems, concomitant medication or medical conditions, mental health concerns
• British Menopause Society has a useful tool for clinicians on the use of testosterone replacement in menopause
• No testosterone products are licensed in the UK for female use. The use of testosterone in postmenopausal women is an unlicensed indication and should be discussed with patients before starting treatment. The use of testosterone will only be in conjunction with hormone-replacement therapy.   
• Doses used in postmenopausal woman are significantly lower than those used in male patients.  
• Baseline and follow-up serum testosterone monitoring may be recommended in line with local and regional guidance (in development); in the meantime, use in line with British Menopause Society guidance