Certain types of hormone replacement therapy (HRT) increase a woman’s risk of endometrial cancer, research suggests.

HRT replaces the natural hormones in the body to relieve unpleasant symptoms of the menopause, such as hot flushes and mood swings.

HRT preparations containing estrogen only increase the risk of endometrial cancer. To reduce the risk, many women take combined estrogen-progestagen preparations or tibolone - a synthetic steroid with hormonal activity. However, little information exists on the risk of womb cancer in users of these therapies.

The new study suggests that HRT with estrogen only or with tibolone increases the risk of endometrial cancer, while the addition of progestagen counteracts that effect. Tibolone is prescribed in many countries outside of the US to treat menopausal symptoms.

In the study, Dr. Valerie Beral, at the University of Oxford, and colleagues collected information on HRT use in approximately 720,000 postmenopausal women who had no history of cancer and had not had a hysterectomy. During an average of 3.4 years follow-up, 1,320 women developed endometrial cancer.

Compared with women who never used HRT, the risk of endometrial cancer was highest in women using tibolone and those using estrogen-only HRT. The risk was lowest among those using continuous combined HRT and was not altered in women who used estrogen with sequentially added progestin, a treatment schedule called cyclic combined HRT.

Cancer risk associated with HRT use varied depending on the woman’s body mass index. Among women who were not overweight, the use of tibolone, estrogen-only, or cyclic combined HRT significantly increased the incidence of endometrial cancer, and continuous combined therapy conferred no benefit.

Among obese women, who are at higher risk of endometrial cancer than non-obese women, tibolone and estrogen-only HRT had little effect on risk, whereas combined HRT significantly reduced the incidence.

The study group points out that the use of combined HRT actually increases the risk of breast cancer compared with estrogen-only. Since breast cancer is more common than endometrial cancer, any benefits associated with the addition of progesterone are outweighed by the risks.

In a related editorial, Dr. Louise A. Brinton and colleagues at the National Cancer Institute in Bethesda, Maryland, point out that women with persistent menopausal symptoms may still require HRT treatment.

Therefore, “for these women and their clinicians, continued research on the long-term risks and benefits of hormone therapy, screening modalities, and effective risk communication remains an important priority.’

SOURCE: Lancet April 28, 2005.