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HRT and cancer - what the papers say

Two major epidemiological studies published today look at the possible increased risk of ovarian and breast cancers associated with hormone replacement therapy (HRT).

A study published early online by the Lancet found that current use of HRT for prolonged periods is associated with a 20% increase in risk of ovarian cancer. The authors used data from the Million Women Study, a large prospective cohort study involving 1.2 million UK women aged 50 and over that is investigating a range of factors that affect women's health. 

The authors calculated that over a five-year period there would be about one extra case of ovarian cancer for every 2,500 users (and one extra death per 3,300 users).

The authors conclude that women who use HRT are at greater risk of ovarian cancer and of death due to it. The risk increases with duration of use: mean duration of use in the study population was 7.7 years and this was associated with a 20% increase in risk. It is related to current use, not past use, and falls back to baseline level soon after use is stopped.

An accompanying comment piece noted the difference between premenopausal use of the same hormones as oral contraceptives, which is protective, and the data on HRT. It is also noted that although the absolute increase in risk is small, the large number of women who used HRT until recently meant that the toll in terms of cancers and mortality was significant.

The second paper reports that the rate of breast cancer in the US fell appreciably in 2003 compared with the rate in 2002. While a number of explanations are possible, the decrease seems to be related to reporting of results from the Women's Health Initiative in 2002 that was followed by a decrease in HRT use among postmenopausal women in the US.

The results of this study show a sharp fall in incidence of 6.7% in 2003 compared to 2002; the incidence stabilised in 2004 with little further decrease. Analysis showed that the decrease actually started in mid-2002 and had begun to level off by mid-2003, and comparison between 2001 and 2004 showed an overall decrease of 8.6%. The decrease was age-specific and occurred only in women aged over 50; there was no significant change in incidence in younger women. It was also primarily in oestrogen-receptor positive tumours.

The authors discuss a number of possible reasons for the changed incidence, but conclude that reductions in HRT use are the most likely. HRT prescriptions in the US declined sharply during 2002 and 2003 and stabilised at a lower level in 2004, from around 60 million to 21 million prescriptions per year.

The MHRA has issued a statement on the two papers. The new evidence is being reviewed by experts, but is unlikely to result in major changes in current advice: this is that HRT is effective for short-term relief of menopausal symptoms but should be used in the lowest effective dose and the minimum duration.

From NeLM Headlines 19/4/07