BMJ  2003;327:767 (4 October), doi:10.1136/bmj.327.7418.767-a

News

HRT may increase risk of ovarian cancer

New York

Treatment for postmenopausal symptoms with oestrogen plus progestogen therapy may increase a woman's risk of ovarian cancer and may also increase the number of endometrial biopsies that women need before cancer can be diagnosed.

Dr Garnet Anderson from the Fred Hutchinson Cancer Research Center in Seattle and colleagues used data from the recently completed women's health initiative (WHI) trial to determine whether hormone replacement was associated with gynaecological cancers or the frequency of diagnostic procedures being performed to rule out cancer ( JAMA 2003; 290: 1739-48[Abstract/Free Full Text]).

The WHI trial followed 16 600 postmenopausal women enrolled at 40 different US clinical centres who had not had a hysterectomy. The women were randomised to two groups, one of which received a placebo and the other a single tablet (0.625 mg/day) of conjugated equine oestrogens plus 2.5 mg a day of medroxyprogesterone acetate. Women who had had a hysterectomy were randomised to a parallel WHI trial of oestrogen alone.

The first trial was stopped early in 2002 because health risks, particularly of an increased risk of breast cancer, were found to outweigh the benefits of the therapy. That study found a risk ratio of 1.26, or a 26% increase (38 v 30 per 10 000 person years) of breast cancer ( JAMA 2002;288: 321-33[Abstract/Free Full Text]). The second trial, in women who had had a hysterectomy, is still ongoing and is expected to be completed in 2005.

In the new analysis by Dr Anderson, after 5.6 years of follow up, oestrogen plus progestogen reduced rates of endometrial cancer by 19% but increased rates of ovarian cancer by 58%. These differences were not significant, however. In total, 27 ovarian cancers were diagnosed per 100 000 women per year in women randomised to the placebo group. With oestrogen plus progestogen, this rate was increased to 42 cancers in 100 000 women per year.

No evidence of a difference was found between treatment groups in the distribution of tumour anatomy, grade, or stage of disease at diagnosis. The authors concluded that the numbers of other gynaecological cancers were too small to make reliable conclusions.

Though combined hormones seem to have a slightly protective effect on endometrial cancer, this therapy does not completely prevent the disease, and the vaginal bleeding that commonly occurs with hormone replacement therapy required women to have additional monitoring. Women in the study randomised to continuous combined hormones were subjected to more endometrial biopsies and vaginal ultrasound scans and were more frequently found to have mild abnormalities in routine Pap tests.

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