Risk of womb cancer now linked to some hormone-replacement therapy

Researchers in the UK say that certain types of hormone-replacement therapy (HRT) increase a woman’s risk of womb cancer while others do not. The study found that though many post-menopausal women, who have not had a hysterectomy, use combined HRT because oestrogen only are thought to increase the risk of womb cancer, little information exists on the incidence of womb cancer in users of these other therapies.

Valerie Beral of Cancer Research UK and Oxford University, 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.

At the follow-up 1320 womb cancers were diagnosed and 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 cancer 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.

Data published in 2003 from the Million Women Study on breast cancer, found that combined preparations of HRT had a much greater effect on a woman’s risk of breast cancer than other types of HRT which creates a dilemma for women who haven’t had a hysterectomy and want to use HRT. On the 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 says Beral.

Louise Brinton and colleagues of the National Cancer Institute, Maryland,US, says the question now is how hormones can be prescribed that will allow women to receive the greatest benefits without commensurate risks.Doctors, in order to minimise the risks should prescribe the lowest possible dose of oestrogen for short periods of time. Recent data suggests that oestrogens prescribed at low doses are generally as 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, other approaches for symptom relief and disease prevention are needed as the menopause progresses.

The study published is published in this week’s issue of The Lancet.

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