The proven benefits of HRT are the relief of menopausal symptoms when taken in the short term and the prevention of osteoporosis when taken over several years. Adverse effects include increases in the risks of breast cancer and venous thromboembolism in current and recent users. The risk of endometrial cancer is increased by unopposed oestrogen therapy in women who have an intact uterus. HRT may increase the risk of ovarian cancer but current evidence is not conclusive. Unlike previously published observational studies, recent randomised controlled trials do not show benefits in terms of secondary prevention of cardiovascular disease and there may be a short term increase in risk of cardiac events in women with pre-existing heart disease.

Overview

Use of HRT in the Northern and Yorkshire region is lower than in England as a whole, with only three Health Authorities in the region ranked in the top 50 nationally for volume and economy of use. This is likely to indicate suboptimal use and women who would derive benefit may not currently be offered HRT.

This article summarises the risks and benefits of HRT in the light of recently published evidence.

Benefits of HRT

Menopausal symptoms

There is substantial evidence that short term use of HRT is effective for the relief of menopausal symptoms and these can have a substantial effect on quality of life.

Osteoporosis

Long term use of HRT should be discussed with women who have risk factors including premature menopause, previous fragility fracture, family history, low body mass index, long term corticosteroid use, loss of height or poor nutrition.

Five to ten years of treatment after the menopause reduces the risk of osteoporotic fracture by almost half. These effects decline rapidly after treatment stops and one trial found a substantially diminished protective effect against hip fracture five years after stopping HRT. The optimum time for commencing treatment and the optimal duration of therapy is uncertain. It should probably be used for at least seven years.

Other benefits

Observational studies have suggested a reduced incidence of dementia in HRT users. However, these may be confounded by selection bias. A randomised clinical trial of HRT in Alzheimer's disease has not shown any benefit. Observational data has also suggested that HRT may prevent colorectal cancer. However available data are inconsistent and data from randomised trials are lacking.

Risks of HRT

Breast cancer

HRT is associated with a slight increase in risk of breast cancer that is restricted to current and recent users and increases with duration of use. No demonstrable risk persists five years after stopping treatment. Among 1000 women who use HRT continually over 5 or 10 years starting at the age of 50, an estimated additional 2 or 6 breast cancers would occur, raising the incidence from 45 cases to 47 and 51 cases respectively. Overall, short term use of HRT for 1-2 years is associated with no appreciable increase in risk.

Endometrial cancer

Patients with an intact uterus should not be prescribed unopposed oestrogen because of the risk of endometrial hyperplasia and cancer. This risk is reduced by co-administration of progestogen for at least 10 to 14 days per month, although it may not be abolished completely. Endometrial protective doses of progestogen are listed in the BNF

Ovarian cancer

The link between HRT and ovarian cancer remains uncertain. In two recently published studies HRT increased the risk of ovarian carcinoma. A meta-analysis of nine case-controlled and one cohort study (n=256,257) showed that HRT taken for ten years was associated with a non-statistically significant increased risk of ovarian cancer. In an observational study (n=21 1,581) post-menopausal oestrogen use for ten years or more was associated with an increased risk of ovarian cancer mortality. These results require confirmation.

Venous thromboembolism

The relative risk of venous thromboembolism (VTE) is raised two to four fold in current users of HRT, but the absolute risk remains low. The absolute risk of VTE is 1 in 10,000 per year in non-users and 3 in 10,000 in users of HRT.

Caution is required when prescribing for women with a personal history of a VTE or a strong family history of the disease.

What about cardiovascular disease?

Observational studies previously suggested that HRT might prevent cardiovascular disease. For example, the Nurses Health Study (n=48,470) found a 44% relative risk reduction in the incidence of major coronary disease in individuals taking HRT.11 However, observational studies may have been confounded by selection bias and there is now evidence from randomised controlled trials that HRT does not prevent cardiac events in women who already have established coronary heart disease.

In the heart and estrogeru/progestin replacement study (HERS)12 (n=2,763) women with established coronary disease and an intact uterus were randomised to receive HRT or placebo. No reductions in cardiac events were observed after a mean follow up of 4 years. (The risk was increased in the first year of treatment.) In the Estrogen Replacement and Atherosclerosis (ERA) study (n=309), both unopposed and opposed HRT did not influence the angiographic progression of coronary atherosclerosis. There is therefore no rationale for the use of HRT in the secondary prevention of coronary heart disease. Use may be justified in women with cardiovascular disease who have a strong indication, but the apparent short term increase in risk of vascular events should be taken into account.

There is currently inadequate evidence on which to recommend HRT as primary prevention of cardiovascular disease and the results of randomised trials are awaited.