Hormone Replacement Therapy - HRT

Can hormone replacement therapy (HRT) reduce the psychological problems that I am experiencing?

Psychological problems including depression and anxiety are often encountered around the time of the menopause and it would certainly seem reasonable to try HRT to assess potential benefit. Psychiatrists distinguish between depressed mood and depressive disorder. Despondency, low spirit and demoralisation are common symptoms that most of us have experienced at one time or another usually as a reaction to one of life's stresses. Depressive disorder is more severe. Loss symptoms, including loss of energy, appetite, interest, libido (sex drive), and the capacity to enjoy life are typical of depressed mood. Depressed mood may respond to HRT but psychiatrists would caution that depressive disorder is generally outside hormonal influence.

Hormone replacement therapy can reduce sleep disturbance, insomnia, increase energy and restore that feeling of well-being. The balance may be redressed so that a woman comes out of despair into a world where she can cope and begin to enjoy her life again. hormone replacement therapy, however,  cannot cure all the stresses and strains of life. One study found that a significant number of women had unrealistic expectations from HRT.

In practice, it may be difficult to predict who will respond to HRT and who will not. There are times when one is sufficiently anxious about a patient's mental state that it seems appropriate to request early psychiatric assessment. However, there is little to be lost by a 'trial' of HRT and perhaps much to be gained. Any improvement is to be welcomed. Adjustment of dosage may provide further benefit. A double-blind (placebo & controlled trials) study found that with oestrogen replacement adaptation to life improved and depression showed signs of lifting and another study concluded that psychological well-being is improved by HRT.

A controlled study (placebo & controlled trials) evaluating HRT for its effect on psychological symptoms found significant improvement in anxiety and depression with oestradiol or combined oestradiol and testosterone implants. This improvement only occurred in women approaching the menopause.

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Can HRT reduce the chance of my developing heart disease?

Women have relatively few problems attributable to coronary heart disease before the menopause because oestrogen during reproductive years confers protection (Q 26.23). The majority of heart attacks before the age of sixty occur in men. After the menopause nature’s protection (oestrogen) is withdrawn. One study found that by the age of seventy, women are as likely to suffer a heart attack as men.

When the ovaries are surgically removed (oophorectomy) before the menopause the oestrogen protection of the coronary arteries is suddenly lost and without hormone replacement therapy the likelihood of heart problems is increased.

To assess the potential benefits of HRT, we have to look at evidence from large on-going studies. In 1976, The American Nurses Health Study recruited 121,700 female registered nurses aged 30-55 years. These women are now aged 54 - 79 years. The latest reports from this study shows reduced incidence of heart problems and deaths from coronary heart disease in association with HRT.

One review of the literature found twenty studies all consistently demonstrating cardioprotection (cardio heart) associated with HRT following oophorectomy. When considering evidence from large studies, we are always concerned that there may have been some hidden bias. It has been suggested, for example, that those nurses thought to be at particular risk of heart disease might have been advised not to take HRT – twenty years ago heart disease was thought to be a contraindication (should not be prescribed). A study specifically designed to exclude such possible bias investigated a case-control analysis of 858 women presenting aged 45-69 between 1986 and 1990 with their first heart attack. The results again showed that oestrogen replacement reduced the risk of heart attack.

Two recently published controlled studies, however, have failed to confirm a beneficial effect of HRT on cardiovascular disease. The Heart and Estrogen/progestin Replacement Study (HERS - 1998) was designed to test the hypothesis that treatment with conjugated equine estrogen 0.625 mg/d with MPA 2.5 mg/d would reduce the combined incidence of nonfatal myocardial infarction (MI) and coronary heart disease (CHD) death compared with placebo in women with prior history of MI, coronary revascularization, or angiographic evidence of CHD. This was the first large-scale randomized clinical-outcome trial of HRT for prevention of CHD in postmenopausal women. After an average of 4.1 years of follow-up, there was no difference in the primary outcome of nonfatal MI and coronary death between the hormone and placebo arms. Numerous explanations have been proposed for the overall null effect of HRT in HERS. These include inadequate duration of follow-up, adverse effects of MPA, bidirectional effects of estrogen (early risk and late benefit), a population of women too old to benefit from therapy (average age was 66.7 years), a preparation of HRT that was not ideal, chance, or that HRT is ineffective in preventing recurrent cardiovascular events in women with established disease. Similarly, The Women's Health Initiative(WHI - 2003) have reported no benefit with HRT on progression of cardiovascular disease.

Interestingly, for those who have been taking HRT for a while, the HERS recommended that "Given the favorable pattern of CHD events after several years of therapy, it could be appropriate for women already receiving this treatment to continue." However, according to HERS II, "Lower rates of CHD events among women in the hormone group in the final years of HERS did not persist during additional years of follow-up. After 6.8 years, hormone therapy did not reduce risk of cardiovascular events in women with CHD. Postmenopausal hormone therapy should not be used to reduce risk for CHD events in women with CHD."

As a result of The WHI and HERS studies, the majority of clinicians accepted that, on current evidence, HRT should not be initiated to reduce the risks of coronary heart disease. The debate, however, continues. Perhaps the major criticism of the HERS study is that the mean age at enrollment was 63 and that the results may not be relevant for those starting in their early 50s.

Five years ago, the investigators of the US Women's Health Initiative (WHI) published their first paper on the effects of hormone replacement therapy (HRT), stating that combined oestrogen/progestogen HRT resulted in increases in coronary heart disease, stroke, blood clots and breast cancer.

This led to widespread adverse publicity about HRT, and to regulatory authorities issuing safety restrictions on its use throughout Europe and the USA. The effect of this was to dissuade both women and their doctors from using HRT, with the results that thousands of women have subsequently suffered from menopausal complaints and may have done untold harm to their future health.

Many international groups of experts, including the British Menopause Society and Women's Health Concern, had expressed disquiet about the initial conclusions of the WHI, and further publications from the same study showed in fact that the risks for coronary disease with combined HRT were not significantly increased, and were actually lower with oestrogen-alone HRT, particularly in the younger age group of 50-59 years.

Menopause and HRT (BMA Family Doctor)

April 2007:2>

A 50-year old patient was found to have a polyp on her cervix and was referred to me by her general practitioner. Her periods had stopped ten years earlier and she had never considered HRT. Bone density scans of her spine and left hip showed that she was at risk of fractures. She was commenced on HRT and remains happily on her regimen. Serial bone density scans have demonstrated the benefit of her treatment (Figure 27.1).

In the Framingham Study, the relative risk (Q33.27) of hip fracture was 0.65 for those who had taken HRT at some time and dropped further to 0.34 for those who had been taking HRT within the last two years. The earlier HRT is commenced the better and it should be continued for at least ten years. There is evidence that bone density remains higher for some years after HRT has been discontinued but the benefit may not be sustained indefinitely.

Following the publication of the Women's Health Initiative (WHI) and the Million Women Study (MWS), regulatory authorities issued an urgent safety restriction on HRT use in preventing post-menopausal osteoporosis, recommending that it now be considered a second-line treatment. Are such recommendations justified? Treatments for osteoporosis, in women with increased future risk for fractures but who have not yet developed the disease, should prevent all types of osteoporotic fractures. Of the available therapies, none other than HRT has been clearly demonstrated to prevent hip fractures in such women. Thus, HRT should be recommended as first-line treatment for osteoporosis prevention. Potential risks of HRT, such as increased development of breast cancer and increased thromboembolism, have long been known. The WHI showed risks in less than 0.3% of women studied, and the MWS appears to have overestimated the risk of breast cancer. Thus, no new safety issues have been identified, and the regulatory authorities may have misinterpreted the data from these recent studies. When given for the correct indications, HRT is of major benefit to many women.

Low dose HRT may be effective for preventing osteoporosis.⁰⁸⁰¹

Calcium supplementation in healthy postmenopausal women is associated with upward trends in cardiovascular event rates. This potentially detrimental effect should be balanced against the likely benefits of calcium on bone.⁰⁸⁰²

Few studies have directly compared different agents or classes of agents used to treat osteoporosis. Although good evidence suggests that many agents are effective in preventing osteoporotic fractures, the data are insufficient to determine the relative efficacy or safety of these agents. Raloxifene, estrogen, and estrogen-progestin increased the risk for thromboembolic events, and etidronate increased the risk for esophageal ulcerations and gastrointestinal perforations, ulcerations, and bleeding.0801

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Would the strength of HRT alter the benefit with osteoporosis?

In a randomised study, 45 postmenopausal women were given a 25mg, 50mg or 75mg oestradiol implant. There was a correlation between the strength of implant, blood levels of oestrogen and effect on bone density. Implants seem to be more effective at increasing bone density than oral oestrogen. In one investigation, ten out of twenty postmenopausal women on long-term oral (tablet) oestrogen therapy were given implants instead. Those changing onto implants increased their bone density by more than 5% whereas those maintained on oral oestrogen did not further improve their bone density.

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Are there treatments other than HRT that may benefit postmenopausal osteoporosis?

Bone density improves with physical activity and diminishes with inactivity. Exercise strengthens your bones. There are other medications notably the biphosphonates but HRT remains the first-line medical treatment.

Would HRT benefit my skin?

Dryness of the skin is a frequent observation following the menopause. The skin texture may improve within a few months of commencing HRT.

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Can HRT help all my menopausal symptoms?

The objectives of hormone replacement therapy are to alleviate or minimise the morbidity (illness) and mortality (death) associated with the reduced levels of reproductive hormones associated with the menopause.

Certainly if your symptoms are solely related to oestrogen deficiency they should respond to hormone replacement therapy. However symptoms typical of the menopause may have a variety of other causes. Lack of energy, soreness of the vagina, and depression are commonly found in association with the menopause, but lack of energy may be related to lifestyle (overdoing it) or anaemia, soreness of the vagina could be due to infection, and depression can have many explanations including the stresses of life.

During reproductive years, the ovaries secrete oestrogens, progestogen and androgens. Following the menopause, there is a significant reduction in production of each of these hormones. Hormone replacement therapy is the term most frequently employed for oestrogen replacement. We should also consider progesterone and androgen deficiency and possible replacement of these (progesterone replacment therapy and Q 28.17).

Unfortunately, many patients or their families, inappropriately assume that there must be a perfect HRT that will provide a complete panacea for all their difficulties; some of their problems may be unrelated to hormone changes. HRT can only reduce symptoms attributable to hormone deficiency.

How prevalent is breast cancer?

Sadly, breast cancer is a relatively common condition; 1 woman in 12 will develop breast cancer at some time during her life (7.5% by the age of 75 years Figure 27.2).

What factors influence the chance of breast cancer development?

It has been shown that natural events can influence the risk of breast cancer. In particular the amount of exposure to the body's own oestrogen is important. Women who have never had children or who had their first child relatively late seem to be more at risk. A girl reaching her menarche (first period) before the age of thirteen has twice the risk of developing breast cancer later in life. There is a doubling of the risk of breast cancer occurring in women who have their last period at age 55 or more compared to those who have a natural menopause before their forty-fifth birthday; the relative risk is greatest beyond the age of seventy. The affect of an early menarche on the risk of later breast cancer development is greater than the effect of a late menopause.

Women who have had an early first pregnancy, those with several children and those who have breast fed seem to be at reduced risk. There has been a suggestion that termination of pregnancy may increase the risk of breast cancer later in life. Surgical menopause (removing the ovaries) before the age of 35 reduces the risk of breast cancer occurring thirty or more years later by more than 60%. These associations would all suggest a plausible link between exposure to oestrogen and breast cancer. Exposure to oestrogen may increase the risk of breast cancer, but it is exposure in the early years that influences the outcome far more than oestrogen in later life. In developed countries including Europe and North America, the trend has been for the menarche (first period) to occur earlier.

Even when considering natural risk factors for breast cancer, there is a lack of consistency between studies. One group, for example, found no correlation between early menarche (first period) or late menopause and the risk of the disease. There has been dispute as to whether a family history of breast cancer increases the risk of developing the disease. Furthermore, we do not have sufficient information to know whether a combination of a family history of breast cancer and HRT significantly increase your risk of developing the disease. Some studies show no difference and others have found an increased risk. 

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What is the relationship between HRT and breast cancer?

For many years there has been debate about the relationship between HRT and Breast Cancer. Until 2003 the risk seemed to be relatively small unless the HRT was taken for more than 10 years. The "Breast cancer and hormone-replacement therapy in the Million Women Study" has provided strong evidence that the risk is greater for those women taking oestrogen and progestogen regimens than had been previously believed. Progestogens must be prescribed for those women taking HRT who have not had a hysterectomy. For women who have taken oestrogen only HRT for 10 years there is an additional 0.5% risk of breast cancer by age 65 and for those who have taken oestrogen-progestogen the additional risk is 2%. This compares to an underlying risk of breast cancer developing for never users of HRT of 4.8%.

Even a small additional risk of breast cancer would potentially affect a large number of women. There have been many studies comparing the incidence of breast cancer in women who have taken HRT and those who never have. Some studies suggest a decreased incidence of breast cancer with HRT and others show an increase. Many of the studies have not been controlled (placebo & controlled trials) for factors already known to influence the chance of breast carcinoma developing (Q 27.14). Consideration should also be given to the age of commencing HRT, duration of therapy, type of therapy and dosage.

Many patients wish to take HRT for just a short time to overcome the acute symptoms of the menopause. There is virtually universal agreement that if HRT is taken for less than five years, there does not appear to be any additional risk.

A progestogen is required for women taking oestrogen unless they have had a hysterectomy (HRT and progestogen). In an early report, there seemed to be reduced incidence of breast cancer for women taking progestogen. A study reported in The Lancet in 1991 showed an apparent better outcome for premenopausal women with breast cancer if surgery was performed during the luteal phase (Q 2.13) of their menstrual cycle: It is during this phase that the ovaries are releasing progesterone (Figure 2.3). The authors conjectured that progestogen therapy may be beneficial before the menopause to counteract the prolonged unopposed oestrogen secretion that is common at that time (Q 24.17B). From a theoretical point of view, however, it is believed that progestogens are unlikely to reduce the risks of breast cancer. The latest evidence from the Nurses Health Study (Q 27.25) indicates no benefit from progestogen in relation to breast malignancy among postmenopausal women.

Recent evidence is tending to indicate a small increased incidence of breast cancer for women currently taking HRT for more than 10 years but not for women who have stopped it after ten years. A meta-analysis (Q33.23) of 51 investigations was published in The Lancet in October 1997. The results were based on data from 160,000 women. More than 900 of these women had been on HRT for at least 15 years.Figures 27.2 and27.3 show the estimated cumulative percentage of women who will develop breast cancer to be expected in those who do not use HRT and for those taking it for 5, 10 or 15 years commencing age 50 or 55. The meta-analysis confirmed that there is a slightly increased incidence of breast cancer related to duration of use.

It should be emphasised that if there is a link between prolonged use of HRT and breast cancer it relates to the chance of the disease occurring rather than to the risk of death from the disease. Women who have been found to have breast cancer whilst on HRT tend to have the diagnosis made at a relatively early stage (Q32.02) probably because of increased surveillance from those prescribing it. This should confer a better long-term prognosis. Death rates from breast cancer in patients taking HRT is lower with risk ratios (Q33.27)Quoted between 0.5 and 0.8. Current users of HRT who have been on treatment for more than 15 years have a 40% reduction in overall death rate from all cancers including breast cancer and from arterial disease. Cancer of the ovaries and body of the womb occur less frequently in HRT patients. We must carefully scrutinise all new data but at the moment the evidence is reassuring.

The recommendation by the data and safety monitoring board to stop the trial by the Women's Health Initiative Investigators (WHI)  because the risk of invasive breast cancer with oestrogen plus progestin was slightly increased has led to inappropriate anxieties for many women currently taking HRT and for those who have been considering it.

There are four fundamental difficulties encountered when interpreting the report. Firstly, the age range of the women in the study was 50 to 79 with a mean of 63.3 years. Only 33% of the women were in the age range 50 to 59 and this is the group who are most likely to consider hormone replacement therapy. Secondly, 20% of the women had taken HRT, for an unspecified duration, before entering the study. Previous HRT may have reduced some of the risks in the placebo arm of the trial. Furthermore, HRT taken for more than 10 years increases the risk of breast cancer by 1.5%. Is it possible that some of the increased breast cancer seen in the HRT arm of the study (38 vs 30 per 10,000 person-years) could be associated with the HRT being taken for several years before entry into the study in addition to a maximum of 8.5 years during the study? The third problem relates to a 40% overall drop out rate but these do not appear to have been excluded from the analysis. Finally, during the study, 10.7% of women in the placebo group started HRT.

It would be beneficial if the WHI could look at outcomes for women in their three age groups (50-59 [33%], 60-69 [45%] and 70-79 [21%] years). It may be that for the younger age groups the risks of HRT are insignificant and for them the trial has been brought to an inappropriate premature conclusion. We must learn from history. In the 1990s many women stopped taking third-generation combined oral contraceptive pills on the advice that the second generation were safer. The result was an increase in pregnancy termination . The third-generation pills were reinstated to first line status as the outcome differences were extremely low.

The majority of perimenopausal women take HRT for symptom relief only. Older women commence HRT predominantly to prevent osteoporosis rather than cardiovascular complications. For the majority of HRT users, the WHI trial confirms that the risks of HRT are low and the benefits are likely to be greater.

The "Breast cancer and hormone-replacement therapy in the million Women Study" must be seen as strong evidence that there is a significant increased risk of breast cancer developing in current HRT users. More than a million women aged 50-64 years were recruited between 1996 and 2001. Half the women had used HRT. Current users of HRT were more likely than never users to develop breast cancer. Past users of HRT were not at increased risk. The incidence of breast cancer was significantly increased in preparations containing oestrogen only. The magnitude of the associated risk was substantially greater for oestrogen-progestogen combinations and for tibolone than for other types of HRT. In current users of HRT the risk of breast cancer with increasing duration of HRT use. Ten years of HRT use is estimated to result in five additional breast cancer per 1000 users (0.5% increase).

There is some evidence that transdermal HRT has a lower risk of breast cancer than other modes of administration.⁰⁸⁰¹ Transdermal opposed estrogens, unopposed estrogens and tibolone do not increase this risk of breast cancer.⁰⁸⁰²

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I have had breast cancer. Is HRT absolutely contraindicated?

It is generally believed that for women who have had breast cancer, HRT is contraindicated. We now recognise that the Question of the safety of HRT for women treated for breast cancer requires urgent attention. There are millions of women in the world who have had breast cancer successfully treated. In 1997 180,000 women were diagnosed and treated for the condition in the USA and it has been estimated that 97,000 of these have only a very small chance of recurrence.

One must always consider risks and benefits. There is a trend for oncologists (cancer specialists) to recognise that the risks of HRT for those with a history of breast malignancy has been overstated although there is likely to be a small, but so far unquantified, risk. There is certainly some early reassuring data indicating that continuous combined HRT carries a lower risk of tumour recurrence than had previously been anticipated. It would, therefore, be inappropriate to rule out HRT for a woman with distressing symptoms adversely affecting the quality of her life. Many women are successfully treated for breast cancer and later on suffer debilitating oestrogen deficiency symptoms or risk premature heart problems or hip fractures from osteoporosis. Recent studies provide encouraging findings and prospective studies have commenced to evaluate the benefits and risks. A history of breast cancer can no longer be considered as an absolute contraindication for HRT although there continues to be some controversy. It is our routine policy when counselling such a patient to liaise with other clinicians involved in her care before commencing treatment. This ensures that the patient receives consistent advice.

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I started HRT early (30-45). Does this affect my risk for breast cancer?

This is a key issue for many women who start HRT early either because they have had an early menopause (Q 26.8) or they developed menopausal symptoms before the menopause. There is no information in the literature to provide us with a precise answer probably because there have been too few women in this group to study adequately. We must, therefore, extrapolate from the facts that are available:-

A woman who has a premature menopause and does not receive HRT has reduced risk of developing breast cancer.

A woman who has a late menopause has a slightly increased risk (Q 27.14).

If a woman has her menopause at the age of fifty and then takes HRT for 15 years, her risks of breast cancer are increased by 1.5% above the underlying risk (Q 27.15)

Let me illustrate this by inventing identical twins. One, Anne, has her ovaries removed at the age of thirty-five and the other, Brenda, has a natural menopause at the age of fifty. If Anne never took HRT she would be less likely to develop breast cancer than Brenda but if Anne commenced HRT at the time her ovaries were removed and continued with it to the age of fifty, we suspect that their risks of developing the disease would be the same. The HRT is essentially replacing her natural oestrogens. If Anne started HRT at the age of thirty five and Brenda took HRT from the age of fifty and they both continued with it to the age of sixty-five each would increase their risk by 1.5%. We do not have any evidence to suggest that Anne would be more at risk than Brenda.

Does HRT increase the risk of cancer of the uterus?

The two most common types of cancer of the womb arise from the cervix or endometrium. HRT is not a risk factor for cancer of the cervix. Cancer of the lining of the womb (endometrial cancer - Q32.20) tends to present with irregular bleeding and at examination the neck of the womb appears healthy. Before cancer develops in the endometrium there are pre-malignant changes and these may occur in association with prolonged episodes of unopposed oestrogen (eggs are not being released in a lady who has not reached her menopause). Irregular bleeding and heavy periods, particularly in women over the age of forty require investigation to exclude pre-malignant changes, usually by hysteroscopy and D and C (hysteroscopy D and C).

We now know that for women who have not had a hysterectomy, it is essential to provide progestogen to prevent the risks associated with unopposed oestrogen. The combination of oestrogen with progestogen, as currently recommended, has been shown to reduce the chance of endometrial cancer developing to below the risk for women who never received HRT. Sadly, when HRT was first used about forty years ago, many women were given oestrogen alone and their chance of developing endometrial cancer was increased eight-fold.

I have had cancer of the uterus. Can I take HRT?

Officially endometrial cancer is a contraindication for HRT although the risks have probably been overstated. The traditional advice that HRT is contraindicated is based on the knowledge that unopposed oestrogen predisposes to the cancer developing (endometrial cancer).

The majority of women found to have endometrial cancer present at an early stage and are likely to be cured by hysterectomy. Following successful surgery, many women subsequently develop debilitating menopausal symptoms which may not always respond to non-hormonal treatment. There are reports of such women receiving HRT and the results have been reassuring. One study reported a better outcome for such women receiving HRT than the controls who did not.

If a woman with a history of endometrial cancer develops symptoms that warrant HRT, the team of doctors responsible for the treatment of the cancer, including the gynaecologist and radiotherapist (doctor specialising in radiation treatment), should liaise to ensure consistency of advice. If HRT is to be prescribed it would seem appropriate to administer progestogen as well as oestrogen.

A nurse had a total abdominal hysterectomy (hysterectomy) and removal of both ovaries for endometrial cancer. When hot flushes became intolerable she elected to start HRT and she has continued to take it without problems for the last twelve years.

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Does HRT alter the risk of ovarian cancer?

We know that the combined oral contraceptive pill undoubtedly reduces the risk of ovarian cancer but the evidence with HRT is not quite so conclusive. For those patients who have had cancer of the ovary, HRT does not seem to cause any adverse effects.

I have had a DVT or pulmonary embolism. Can I take HRT?

Until just a few years ago hormone replacement therapy - HRT - was contraindicated for women who had a history of a clot in a leg vein or the pelvis (deep venous thrombosis) or a blood clot that had travelled to the lungs (pulmonary embolism): A pulmonary embolism can be fatal. It was known that the combined oral contraceptive pill increased the risks (Q15.14) and as HRT also contained oestrogen it was assumed that the risks would be too high. The changes in the blood clotting mechanism seen with the combined oral contraceptive pill, however,  have been shown to be minimal with HRT and for the last ten years HRT has no longer been contraindicated. The pendulum always seems to be swinging. The latest recommendation is to avoid HRT as far as possible when there is a history of Deep Venous Thrombosis or Pulmonary Embolism.

Soon after my appointment as a consultant, I was asked to see a lady of seventy who was a piano teacher. She had been taking HRT for ten years and she was certain that this maintained her mental ability and dexterity. Sadly, she sustained a DVT and required Warfarin to thin her blood. The physicians had appropriately stopped her HRT but some months later she wanted to recommence it. We were reluctant to go against the rules although the evidence about the risks in this situation wasQuite reassuring. The lady explained that without her HRT she could not play the piano never mind teach it. She promised me that, even if she died from her HRT she would not consult her lawyers! My legal advisers assured me that provided the patient was fully aware of the implications, I was entitled to prescribe HRT for her from a medico-legal point of view. Happily, she attended my clinics for many more years and no doubt played and taught beautiful music.

A 50-year old lady, who's last period had occurred 7 years earlier, was referred to me for consideration of hormone replacement therapy. Before the age of 40 she had five episodes of deep venous thrombosis. A 'thrombophilia screen' demonstrated a predisposition to thrombosis. Our haematologists (specialists in disorders of the blood) commenced her on Warfarin which reduces blood clotting and she was then started on HRT without problems.

In 1996, three papers appeared in 'The Lancet' indicating a small increased risk of thromboembolism in current HRT users. We know that the risk of thromboembolism is 1 person in 10,000 per year and the risk of dying from a thromboembolism is 1 in a million. HRT increases these risks three-fold that is to say that the risk of dying from a blood clot as a result of the HRT is 3 in a million per year. This risk should be seen in the context of other causes of mortality (Figure 27.4). The risks of dying from an accident are not high but your risk of dying from an accident are greater than your risk of dying from pulmonary embolism. The Committee on Safety of Medicines has commented that this new data does not change the overall positive balance between the benefits and risks of treatment for most women.

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I have varicose veins. Can I take HRT?

Varicose veins are a common problem. Provided they are not causing pain, there is no reason to withhold HRT. If the veins are causing pain medical assessment is indicated.

Should HRT be stopped before I have an operation?

One of the potential complications following an operation is a blood clot in one of the veins in the legs or pelvis (surgery risks) and we surgeons try to reduce this risk as far as possible. Whereas the advice for those on the combined oral contraceptive pill is that they should stop taking it four weeks before surgery, the advice with HRT is less defined. Many gynaecologists frequently introduce an oestradiol implant at the time of hysterectomy (hysterectomy). You should let your surgeon know that you are taking HRT so that you can receive the appropriate advice.

Does HRT affect life-expectancy?

The balance of evidence, in my opinion, suggests that HRT increases life-expectancy. In the Leisure World Laguna Hills study, there had been 1447 deaths after 7.5 years follow-up. Mortality was reduced by 20% in those who had taken HRT at some time in their lives. For current users who had been taking HRT for more than 15 years there was a 40% reduction in overall mortality. There were less cancer-related deaths in the HRT group. In a meta-analysis (Q33.23) of the literature published in 1992, it was calculated that in general there would be a net gain of one year for a woman starting HRT at the age of fifty. For those women most at risk of coronary heart disease, HRT would provide a net gain of two years. For women at particular risk of developing breast cancer, HRT would still provide a net gain of one year.

The American Nurses Health Study has followed 121,700 female nurses from 1976. Their latest report (1997) has continued to show lower death rates at a given age in HRT users.

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I am still seeing my periods. Could I benefit from HRT?

It is possible that you may have menopausal symptoms such as hot flushes (hot flashes), night sweats, sleeping problems or mood changes associated with the menopause even before your periods have stopped. You may well reap the benefits of HRT and there is really nothing to lose by giving it a trial.

I have fibroid