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There are no simple answers to questions about HRT

Ann McPherson
cbe
MB BS FRCGP FRCP DCH
Co-author of Women's Health in General Practice (Oxford University Press GP series) GP
Oxford
Chair
Adolescent Task Force
RCGP
Medical Director
DIPEx
Department of Primary Health Care
Institute of Health Sciences
Oxford

As a primary care professional, your answers to your menopausal patients are influenced by evidence-based information, or lack of it, clinical experience, belief and personal prejudice.

So how does a perimenopausal woman make a decision about about HRT, and how does a GP help her in the process? In recent years in our society, there has been a shift from "grin and bear it" to a "medicalise/fix the fault" school of thought.

To take or not to take HRT?
There are two main reasons for a woman going through the menopause to take HRT. The first is to control symptoms, and the second is to prevent long- term health problems.

Control of symptoms
Over 75% of menopausal women will experience hot flushes; night sweats is the next most common symptom, followed by vaginal dryness and sleeping problems. There is good evidence that HRT will control all these symptoms, often with improvement beginning in the first week of treatment, though it may take up to three months.

Prevention of long-term health problems Osteoporosis  All women will, in the long run, lose bone mass, and up to one in three will be classified as osteoporotic. There is good evidence that while (and only while) a woman takes HRT, it will prevent osteoporosis. However, the evidence that HRT protects against fractures is more limited, though it does decrease the number of fractures expected.

Cardiovascular disease and stroke  There is much confusion as to the part played by oestrogen with or without progestogen and the influence on cardiovascular disease. Although it has been argued that theoretically oestrogen is protective, and early epidemiological studies supported this view, more recent clinical trials and overviews appear to show an excess risk of ischaemic heart disease in those on HRT, especially in those women who already have coronary heart disease. Therefore at ­present there is no evidence to prescribe HRT to protect against heart disease. Similarly, the most recent randomised controlled trial does show an increase in the number of strokes amongst women on HRT.

Memory loss and dementia  To date there is no good clinical trial evidence that HRT slows or reduces memory loss or dementia, though some of the trials do show conflicting evidence.

Quality of life, mood and depression  There is much anecdotal evidence of improvement in this area as well as some short-term clinical trial support. The latter shows that these areas are particularly improved when vasomotor symptoms and sleep problems have been relieved.

Problems associated with taking HRT
At the mild end, these include weight gain, breast tenderness, bloating, headaches, mood swings, nausea and premenstrual syndrome. The objective evidence for weight gain is poor, though it is the main reason cited by women for stopping HRT. Around 5-10% of women complain of some of these problems. A change in preparation, using a different progestogen or route of administration, can often get rid of the problem and should be tried. The more serious problems associated with HRT include venous thrombosis, breast cancer and uterine cancer.

Venous thromboembolism
The background level of venous thromboembolism has been estimated as one in 10,000. HRT does double this risk to one in 5000, though a recent study of women with established heart disease has put the increased risk as higher than this. Most of the increased risk appears to be in the first year of use.

Breast cancer
It has been estimated that there are an extra 3-9 extra cases of breast cancer per 1,000 women for 10 years of HRT use, and an additional 5-20 cases per 1,000 women for 15 years of use, though the numbers may be greater than this. It is claimed that the breast cancers in women taking HRT are more likely to be in situ, node-negative, oestrogen receptor-positive, and to have a better prognosis than non-HRT-associated breast cancer. There appears to be no excess risk of breast cancer five years after stopping oestrogen.

Endometrial cancer
Users of unopposed oestrogen who still have their uterus are more likely to develop endometrial hyperplasia, with a fivefold-increased risk of developing endometrial cancer after five years' use. The inclusion of progesterone in the therapy, either cyclically or ­continuously prevents this excess risk, but not all women can tolerate the progesterone.

Other cancers
Most, though not all, studies do not show any increase in colon cancer and ovarian cancer associated with HRT use.

Gall bladder disease
The risk of gall bladder disease in women who take oral oestrogen is about double that of nonusers, which runs at about 8%, although observational studies indicate that this is not the case in those women using the transdermal route of administration.

What HRT to take?
There are many different preparations - pills, patches, gels, creams, vaginal creams and implants; pills containing different types of oestrogen and different types of progesterone, patches with and without a progesterone, and all of these available as cyclical or as continuous preparations.

The starting point is whether the women has had a hysterectomy. If she has had a hysterectomy (and this applies to 20% of women), the decision is facilitated as there is no risk of developing uterine cancer from taking oestrogen alone. The oestrogen alone is given as a pill, a patch or, more rarely, an implant.

If she has not had a hysterectomy, the question which influences the choice of preparation is whether she is at the menopause or a year postmenopausal.

Women with a uterus who are going through the menopause need to take a preparation that continues to give them regular periods. This consists of daily oestrogen and usually 12 days of progestogen per month. Most women will get a period (withdrawal bleed) at the end of the progestogen course.

A year or so after the menopause, it is possible to take a different preparation that gives no periods. This consists of daily oestrogen and daily progestogen taken continuously throughout the month. Trying to take a continuous preparation earlier tends to cause light or irregular bleeding.

The decision whether to prescribe pills, patches or creams and which oestrogen or progestogen to use is very much a case of try it and see which suits the patient best. Most women try pills first and if there are side-effects will try a different progestogen or move to a patch.

Women whose main problem is vaginal dryness may get sufficient relief of symptoms from the use of oestrogen vaginal creams, which are poorly absorbed and reportedly not associated with the other possible concerns from taking unopposed oestrogen, such as uterine cancer.

When to start to take HRT?
There are almost no absolutes about when to start HRT. There are, however, certain women who should definitely consider taking it. These include women having an early menopause (before 45 years), women who have had their ovaries removed and women with severe menopausal symptoms.

The list used to include women with osteoporosis or a strong family history of this condition, but there are now alternatives to HRT on offer. Some women want to start as they approach the menopause, while others want to wait till they have severe symptoms.

How long to take and when to stop?
Once again there is no right answer for all women. Women in the UK have tended to take HRT for two to three years, though recently more women have been encouraged to take it for longer. In the light of the recent research, this cautious approach to HRT has in retrospect appeared to be sensible strategy.

Weighing up the risks and benefits
There are both advantages and disadvantages to taking HRT. It is not the panacea for all women that some thought it might prove to be, though it will certainly continue to play an important role in helping some women go through the menopause.

How an individual woman will make the decision will be affected by her own views of the pros and cons and the accuracy of the information she is provided with.

In the light of recent research from the USA, which showed a 26% increase in heart disease and angina, a 26% increase in breast cancer, as opposed to a 24% reduction in fracture risk, it is likely that the whole field of the long-term prescribing of HRT will need a reassessment.

Further reading
Barrett-Connor E. Circulation 2002;105:902-3.
Grady D, et al. Ann Intern Med 2000;132:689-96.
Hemminki E, McPherson K. BMJ
1997;315:149-53.
Hlatky MA, et al. JAMA
2002;287:591-7.
Ross RK, et al.
J Natl Cancer Inst 2000;92:328-32.
Schairer C, et al. JAMA 2000;283:485-91.
Siris ES, et al. JAMA
2001;286:2815-22.
Women's Health Initiative Randomised Controlled Trial. JAMA 2002;288:321-33.