Risk of womb cancer varies according to the type of HRT used


EMBARGO: 00:01H (London time) Friday April 29, 2005. In North America the embargo lifts at 6:30pm ET Thursday April 28, 2005.

Certain types of hormone-replacement therapy (HRT) increase a woman's risk of womb cancer while others do not, concludes a study published in this week's issue of THE LANCET.

Many post-menopausal women, who have not had a hysterectomy, use combined HRT (containing progestagen and oestrogen) or tibolone (synthetic HRT), because oestrogen-only preparations are known to increase the risk of womb cancer. But little information exists on the incidence of womb cancer in users of these other therapies.

Valerie Beral (Cancer Research UK and University of Oxford) and colleagues recruited 717, 000 postmenopausal women from the UK, aged 50-64 years, who had no previous history of cancer and had not had a hysterectomy, into the Million Women Study, between 1996 and 2001. The women filled in questionnaires about their use of HRT and other personal details and were followed up for an average of 3.4 years. Just under half of the women reported that they had used some form of HRT.1320 womb cancers were diagnosed at follow-up.

The investigators found that, compared with women who had never used HRT, women who last used oestrogen-only HRT or tibolone had a higher risk of womb cancer overall and that the risk increased with longer use of tibolone. By contrast, use of combined HRT did not increase the overall incidence of womb cancer. The researchers also found that among HRT users the risk of womb varied according to bodyweight when compared with women who had never used HRT. In women who were not overweight, a form of HRT, called cyclic-combined HRT, also increased the incidence of womb cancer. In obese women (who normally have a substantially higher incidence of womb cancer than non-obese women), use of both continuous and cyclic combined HRT significantly reduced the incidence of womb cancer, whereas tibolone and oestrogen-only HRT had little additional effect on incidence.

In August 2003, The Lancet published data from the Million Women Study on breast cancer (Lancet 2003: 362: 419-427). The study found that combined preparations of HRT had a much greater effect on a woman's risk of breast cancer than other types of HRT.

Professor Beral concludes: "These new results create a dilemma for women who haven't had a hysterectomy and want to use HRT. On one hand, oestrogen-only HRT and tibolone increase the risk of endometrial cancer but, on the other hand, HRT containing both oestrogen and progesterone causes the greatest increase in breast cancer. Since breast cancer is much more common than endometrial cancer, combined HRT poses the greatest overall cancer risk."

In an accompanying comment Louise Brinton and colleagues (National Cancer Institute, Maryland, USA) state: "The important clinical question is how hormones can be prescribed in a fashion that will allow women to receive the greatest benefits without commensurate risks. To minimise cancer and other risks, clinicians should prescribe the lowest possible dose of oestrogen for short periods of time. Fortunately, recent evaluations support the idea that oestrogens prescribed at low doses are generally effective in controlling menopausal symptoms as the traditional higher doses. Although the benefits of short-term use of hormones during the early stages of menopause appear to outweigh the risks, we need other approaches for symptom relief and disease prevention as the menopause progresses."

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