See also separate articles Hormone Replacement Therapy and HRT - Initial Consultation.
Large studies, including the Women's Health Initiative and the Million Women Study, have cast concerns and controversy over the use of HRT with evidence of increased risk of breast cancer, cardiovascular disease and thromboembolic disease and little evidence for supposed benefits such as maintained protection against osteoporosis and cognitive decline.
However, many women still have significant and disabling symptoms associated with the menopause and HRT continues to have an important clinical role in improving quality of life in symptomatic menopausal women, with many opting to remain on HRT despite the research findings. This is reflected by attitudes of UK women doctors to using HRT themselves: whilst uptake and continuation rates have declined since 1993 (reflecting general prescribing trends), many still intend to continue long-term use of HRT.
- For the treatment of menopausal symptoms where the risk/benefit ratio* is favourable, in fully informed women, in the lowest possible dose to control symptoms and for the shortest duration possible.
- For women with early menopause (<45 years) until the age of natural menopause (taken as 50 years).
- HRT should only be used for the prevention of osteoporosis in women unable to use other medicines licensed for this use.
Initial follow-up after starting HRT should occur at about 3 months. Most symptoms are likely to have responded to oestrogen in this time period and any residual problems may require alternative management.
Frequency of follow-up thereafter is controversial and not evidence-based. Drug manufacturers vary in their recommendations but consensus appears to be a minimum of annual checks.
Components to a follow-up assessment:
- Check effectiveness: is there good symptom control? Is the patient receiving adequate oestrogen? A 3-month trial of HRT is suggested to achieve maximum effect. Where a patient remains symptomatic, consider:
- Poor absorption - for example, due to bowel disorder.
- Drug interactions reducing bio-available oestrogen - for example, carbamazepine and phenytoin.
- Problems with patch adhesion.
- Incorrect diagnosis - hypothyroidism or diabetes may mimic some features of menopause.
- Patient expectations may also need to be addressed.
- Check for side-effects, eg breast tenderness or enlargement, nausea, headaches or bleeding, and manage appropriately (see below under Management of side-effects).
- Check blood pressure and weight.
- Breast examination - only necessary if clinically indicated (based on symptomatic disease, personal or family history) but encourage breast awareness and participation in screening mammography if appropriate for age.
- Pelvic examination - as suggested by patient or family history and includes cervical smear if due and appropriate for age (20-64 years).
- A review and discussion of an individual's risk/benefit ratio concerning HRT should occur at least annually. Explain that some of the risks (eg breast cancer, ovarian cancer) increase with longer duration of HRT. Alternatives to continuing on HRT, including stopping or a trial of an alternative approach for symptom control, should be discussed.
- If appropriate, consider switching from cyclical HRT to continuous combined HRT (see below).
Side-effects account for 35% of HRT discontinuations. These may be oestrogen-related (occurring continuously or randomly through a cycle) or progestogen-related (occurring cyclically during progestogen phase).
- Add notes to any clinical page and create a reflective diary
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Oestrogen-related side effects
These are usually transient and resolve spontaneously with increasing duration of use. Encourage patients to persist with a particular therapy for at least 12 weeks. Side-effects are more likely to occur or be problematic where there has been a longer interval since ovarian failure. Oestrogen-related side-effects include:
- Breast tenderness or enlargement - try a low fat, high carbohydrate diet. Evening primrose oil is no longer recommended.
- Leg cramps - try exercise and calf stretching.
- Nausea and dyspepsia - adjust time of dose, and administer with food.
- Headaches - try transdermal oestrogen, as this may produce more stable oestrogen levels.
For side-effects persisting beyond 12 weeks:
- Reduce the oestrogen dose (though this may limit original menopausal symptom control).
- Change the oestrogen type, ie between estradiol and conjugated oestrogens.
- Change the route of delivery.
These may be more problematic and are usually connected to the type, duration and dose of progestogen. They include:
- Fluid retention
- Headaches or migraine
- Breast tenderness
- Mood swings and depression
- Lower abdominal and back pain
Again encourage perseverance, as symptoms may improve over 3 months. If there is no improvement, strategies include:
- Change of progestogen type.
- Reduce dose (but not below recommended ceiling required for endometrial protection).
- Change route away from oral therapy.
- Reduce duration of therapy - change from a 14-day progestogen to a 12-day monthly sequential replacement regime.
- Reduce frequency, using long-cycle HRT - this is progestogen for 14 days every 3 months (only suitable for women without natural regular cycles).
- Use of continuous combined therapy or tibolone often reduces progestogen-related side-effects with established use (only suitable for postmenopausal women).
This is often given as a major reason why women discontinue HRT but there is no RCT evidence of HRT-induced weight gain. Reassure that weight gain is common at this time of life and counter with dietary and lifestyle advice.
Monthly sequential preparations should produce regular, predictable and acceptable bleeds starting towards the end, or soon after, the progestogen phase. This pattern may be altered by:
- Drug interaction
- Gastrointestinal upset
Breakthrough bleeding is common in the first 3-6 months of continuous combined and long-cycle HRT regimens.
- In perimenopausal women with an intact uterus (usually taking cyclical combined HRT)
- There is a change in pattern of withdrawal bleeds or a change in pattern of breakthrough bleeding.
- There is breakthrough bleeding that persists for more than 4-6 months or does not lessen while taking a 3-monthly regimen.
- There is persistent or unexplained bleeding after cessation of hormone therapy for 6 weeks.
- In postmenopausal women with an intact uterus (usually taking continuous combined HRT)
- Breakthrough bleeding persists for more than 4-6 months after starting HRT or tibolone.
- A bleed occurs after amenorrhoea.
- There is persistent or unexplained bleeding after cessation of hormone therapy for 6 weeks.
Before changing treatment due to bleeding, always:
- Perform a full pelvic examination, visualising the cervix.
- Check smears are up-to-date.
- Refer for transvaginal ultrasound to exclude pelvic abnormalities.
Where pelvic pathology is excluded, strategies for tackling bleeding problems include:
- Heavy or prolonged bleeding - increase dose, duration or type of progestogen. Consider the use of the levonorgestrel-releasing intrauterine system (IUS) combined with oral or transdermal oestrogen.
- Bleeding early in progestogen phase - increase dose or change type of progestogen.
- Painful bleeding - change type of progestogen.
- Irregular bleeding - change regimen or increase progestogen.
- No bleeding - occurs in 5% of women and is due to an atrophic endometrium. Need to exclude pregnancy in perimenopausal women and to ensure compliance with the progestogen element of the HRT regimen.
Switching from cyclical HRT to continuous combined HRT
Cyclical HRT can be changed to continuous combined HRT when the woman is considered to be postmenopausal. This is generally:
- Women older than 54 (about 80% of women are postmenopausal by this age).
- Women who experienced 6 months of amenorrhoea or had increased follicle-stimulating hormone levels in their mid-40s. Such women are likely to be postmenopausal after taking several years of cyclical HRT.
Menopausal symptoms (hot flushes and sweats) last on average between 2-5 years but there is considerable individual difference and they may last decades in some women. A trial of withdrawal of HRT should be considered in:
- Those women symptom-free on HRT after 1-2 years.
- Women who have been on HRT for longer than 5 years.
- Women on HRT for premature menopause after the age of 50.
See paragraph about alternatives to HRT at the bottom of the management of menopause article.
Abrupt cessation or gradual withdrawal of HRT?
Little good evidence to guide practice is available. Many women do not notice symptoms even with an abrupt cessation, whilst others revert swiftly to their original problems with hot flushes, sweats and sleep disturbance. Some experts suggest gradual reduction of HRT dose:
- Oestrogen-only tablets - decrease from 2 mg to 1 mg daily for 1-2 months and then take on alternate days for a further 1-2 months.
- Oestrogen-only patches - gradually reduce patch strength to 25 micrograms daily by reducing a patch strength every month. Half a 25 microgram patch can then be used for a further 1-2 months.
- Cyclical combined tablets - step down to pack containing 1 mg estradiol daily for 1-2 months, then cut the tablet in half for 1-2 months and throw away the unused half. This ensures that the women still gets progestogen.
- Cyclical combined patches - gradually reduce the patch strength as for oestrogen-only patches but ensure use of oestrogen-only patches for just 2 weeks of cycle and combined patches for the next 2 weeks.
- Continuous combined tablets or patches - reduce dose gradually to the lowest strength of tablets or patches and then use half a tablet daily or half a patch for a further 1-2 months.
Vasomotor symptoms frequently recur on stopping HRT and, where severe, restarting treatment may be the most appropriate course of action.
Further reading & references
- Roberts H; Managing the menopause. BMJ. 2007 Apr 7;334(7596):736-41.
- Summary of Global Summit on menopause related issues, March 2008; International Menopause Society
- Nelson H; Menopause. Lancet. 2008 Mar 1;371(9614):760-70. Review
- Rossouw JE, Anderson GL, Prentice RL, et al; Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized controlled trial. JAMA. 2002 Jul 17;288(3):321-33.
- Beral V; Breast cancer and hormone-replacement therapy in the Million Women Study. Lancet. 2003 Aug 9;362(9382):419-27.
- CSM Drug Safety Update Vol 1, Issue 2, Sept 2007
- Rymer J, Sturdee DW; Hormone replacement therapy after the menopause--where are we now? Br J Gen Pract. 2005 Mar;55(512):172-4.
- Isaacs AJ, Drew SV, McPherson K; UK women doctors' use of hormone replacement therapy: 10-year follow up. Climacteric. 2005 Jun;8(2):154-61.
- Menopause, Clinical Knowledge Summaries (January 2008)
- Hormone-replacement therapy: safety update - UK Public Assessment Report, Medicines and Healthcare products Regulatory Agency (MHRA), July 2007
- Rees M & Purdie DW (eds) Management of the menopause (2nd edition), 2002 BMS publications ISBN 0953633819
- Royal College of Physicians;; Consensus Statement on Hormone Replacement Therapy. October 2003.
|Original Author: Dr Chloe Borton||Current Version: Dr Michelle Wright|
|Last Checked: 23/05/2011||Document ID: 1321 Version: 26||© EMIS|
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