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The negative publicity in the media over the last two or three years has mainly been related to the reported effects of high-dose HRT regimens in asymptomatic women in the US, who were in the Women's Health Initiative Study (WHI) and were aged 63 on average at the start of treatment.

Data from such women is not relevant for the majority of women for whom we are prescribing HRT in the UK ­ that is women aged 45-55 with menopausal symptoms. Such women will benefit from an improvement in their quality of life with relief of flushes, night sweats and improved sleep, especially, and they should be given the opportunity to make an informed decision about whether they wish to try HRT.

However, the women who should be particularly advised to have oestrogen replacement therapy are those who have experienced a spontaneous or induced premature menopause. The average age of the meno-pause in the UK is 51, but if ovarian function ceases before the age of 40 the effects of oestrogen deficiency are often more pronounc-ed. In particular a medical or surgically induced premature menopause with the sudden loss of oestrogen production is almost always accompanied by distressing hot flushes and sweats.

Young women with malignant disease such as Hodgkin's disease or leukaemia may present in their 20s or 30s with ovarian failure resulting from treatment of the condition. Without oestrogen replacement, these women are at significant risk of failing to develop a healthy skeleton and optimal bone density, which is usually reached between the ages of 30 and 40.

They should be advised that oestrogen replacement will help to maintain a healthy skeleton, and that this should be taken at least until the normal age of the meno-pause. All the data about the risks of HRT refers to postmenopausal women and there is no evidence that this applies to women with a premature menopause, so that in terms of duration of HRT and the risks associated, the clock should not be started until the normal age of the menopause.

Many women will experience distressing symptoms due to declining oestrogen production during the climacteric, and while they are still experiencing menstrual periods and potentially fertile. A sequential HRT regimen is usually the most suitable for this situation and is intended to give a regular and predictable bleed while replacing the declining oestrogen production.

While taking this therapy, the time when the menopause would have occurred will be masked. HRT regimens are generally not contraceptive except when a Mirena is being used for the progestogen part of the therapy, so that where appropriate women should be advised of the need for additional contraceptive precautions.

If it is necessary to determine if the menopause has been reached, the HRT needs to be stopped for a few months to see if menstruation resumes, or possibly to monitor the serum FSH level as an indication of ovarian failure.

The standard advice about the use of contraception in relation to the menopause is that when the last period occurs before the age of 50, then contraception should be continued for at least two years subsequently, and for those with the last period after the age of 50, contraception should continue for at least one year.

Menopausal women are frequent users of herbal remedies, vitamin supplements and other so-called natural products, with surveys showing that at least one in three women have used them at some time. There is a lower prevalence of menopausal symptoms in Japan and China where there is a higher dietary intake of soya products which contain phyto-oestrogens.

Many different types of phyto-oestrogen preparations are marketed. Red clover tablets have been promoted particularly, and some randomised trials have suggested a slight reduction in hot flushes. Other herbal remedies such as black cohosh, evening primrose oil, dong quai and ginkgo biloba have all been advocated, but there are no reliable randomised controlled trials to confirm their efficacy.

The mechanism of the hot flush is not fully understood, but the alteration of the thermo-regulatory response that is the basic cause is influenced by stimulation of serotonin (5-HT) receptors in the brain. Several neuro-transmitter modulating agents have been tried and some have had limited success in relieving hot flushes.

Selective serotonin re-uptake inhibitors such as venlafaxine can reduce hot flushes in a dose-dependant manner, but there are often associated side-effects which are unsatisfactory. Clonidine, an alpha-adrenoceptor agonist that has been used for the treatment of hypertension, may be marginally superior to placebo in decreasing hot flushes, but is also associated with side-effects, which may be limiting.

For the prevention of osteoporosis, there is no evidence that phyto-oestrogens have any significant effect. Bisphosphonates such as alendronate, etidronate and risedronate and the new agent strontium ranelate are effective and suitable alternatives to HRT in postmenopausal women.

There is now a wide variety of sources of information concerning the menopause and HRT, but many that may be accessed through the internet in particular are uncontrolled, not peer reviewed and often of limited validity.

Hopefully our patients will seek well-

informed advice from appropriately trained nurses and doctors in primary care, or where there are complicating factors will be referred to a specialist menopause clinic or a recognised expert in the menopause.

There are a large number of menopause clinics and appropriate experts scattered all over the UK, as well as the British Meno-pause Society (BMS). There are also helplines manned by specially trained nursing and medical staff at Women's Health Concern and the Amarant Trust menopause and HRT advice helpline (see page 44).

Many local family planning clinics also provide advice and information and have staff who are trained and experienced in the subject. The BMS together with the RCOG has produced a training module for doctors and nurses who wish to gain specialist knowledge and experience, and it is hoped that in the future there will be at least one person in every general practice who has undergone such training.

A BMS booklet for patients The menopause; what you need to know is available in some branches of Boots or from BMS.

With the recent scares in the media about the risks of HRT, there have been many women who have suddenly stopped taking HRT and have experienced a return of symptoms. Some have been taking HRT for 10 years or more. There is no way of predicting whether the cessation of therapy will be followed by return of symptoms.

Theoretically, a gradual reduction of the dose and a slow weaning off the therapy over several weeks or months may be less likely to be followed by withdrawal symptoms, but there is no data to confirm that such a strategy is preferable.

The advice to women with a return of symptoms will depend on many factors such as the severity, age, type and dose of therapy, and whether there are any perceived increased risks from resuming. However, if the quality of life is significantly impaired, there would be a strong case for resuming the therapy at the lowest effective dose and then reviewing the situation after an interval of six months or more.

In response to all the various reports about the risks of HRT, the regulatory authorities in the UK, Europe and North America have all recommended that HRT should be given at the lowest effective dose. Until fairly recently, the options of dosage change were limited with oral regimens, although the transdermal patches or gels allow for more flexibility in adjusting the dose.

Several studies have now confirmed that 1mg of oestradiol or 0.3mg of conjugated equine oestrogens or 25µg of transdermal oestradiol by patch will provide satisfactory symptom relief for most women, and these are the dosages now being advised for starting treatment. It is unlikely that doses lower than 0.5mg oestradiol or the equivalent will prove to be sufficiently effective for symptom control, but there may still be some effect on prevention of bone loss.

As a general rule, the dose of oestrogen that is required will depend on the age of the woman, and certainly for those with a premature menopause the higher dos-ages will usually be necessary to relieve symptoms whereas for women who are well past the menopause the lowest doses should be used initially and increased only if the response is unsatisfactory.

The rationale for using the lowest effective dose is based on the assumption that the risks of therapy are dose related. Unfortunately there is limited data to support this view.

Having witnessed the extreme distress experienced by some women with severe meno-pausal symptoms, I am quite certain that in the same situation I would wish to be relieved of these symptoms and to improve quality of life by taking HRT.

Vaginal dryness and dyspareunia is another very distressing complaint which is so easily relieved either by systemic or local oestrogen therapy. If I was at particular increased risk of osteoporosis or had proven osteopenia, I would certainly wish to prevent further loss of bone, and initially I am sure that this is best achieved by replacement of the oestrogen deficiency for up to 10 years.

If I had experienced a premature meno-pause I would certainly insist on having oestrogen replacement at least until the normal age of the menopause and probably for some time afterwards.

I am increasingly impressed by the evidence for a window of opportunity around the time of the menopause and immediately afterwards during which if oestrogen therapy is started, there will be a delay in the onset of coronary artery atherosclerosis, and possibly the initial pathological processes involved in the development of dementias such as Alzheimer's disease.

Once these pathological processes have become established there is no evidence that oestrogen therapy will have any benefit, and this was one of the problems with the WHI, which tried to treat or prevent a condition that was established already.

A diagnosis of breast cancer has generally been considered a contraindication for HRT. There is, however, little evidence to support this view and what few prospective controlled studies that have been undertaken have had conflicting results.

The data from WHI indicated that combined oestrogen and progestogen therapy was associated with an increased risk after five or more years of use, but the women who were taking unopposed oestrogen in this study did not demonstrate an increased risk after seven years of use.

The Million Women Study from the UK reported an increased risk with all forms of HRT, though this was much greater with combined therapy. Women who have had breast cancer often experience very distressing menopausal symptoms, either directly due to the menopause or due to the treatment, especially with tamoxifen. Such patients are common referrals to specialist menopause clinics.

Unfortunately alternative non-hormonal remedies are often ineffective or cause

unsatisfactory side-effects. My policy is to discuss the situation and the relative lack of data on the risks of recurrence with HRT, and then to share the problem with her breast surgeon and oncologist.

Opinions from such colleagues vary considerably around the country, with some being supportive of limited low-dose usage of hormone therapy, which is what several of my patients are using. This strategy is as equally unsupported by clinical data as the strategy of denying hormone therapy and might be considered a gamble.

However, as long as the woman is fully informed of the controversies, and she feels that for an improvement in her quality of life she is prepared to take such an unquantifiable risk, I believe it is her right to be able to do so.

Sudden cessation of high-dose hormone therapy is commonly associated with withdrawal symptoms, which is a situation analogous to a pre-menopausal woman who has her ovaries removed at surgery. It is generally advised that to reduce the risk of withdrawal symptoms the dose of HRT should be reduced before complete cessation so that there is more gradual weaning.

However, there is no data to support this practice, and clinical experience indicates a wide variety of responses. Depending on the preparation being used, it is not always practical to reduce the dose. Cutting tablets in half is not satisfactory but patches can be gradually reduced in size.

Tablets can be taken on alternate days and then gradually increasing the gap, and in sequential regimens it is still important to end with the progestogen phase.

If withdrawal symptoms persist, the options are either to put up with them and try alternative non-hormonal strategies or to resume HRT at the lowest effective dose and try again to wean off after a few more months.

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