Women who take hormone-replacement therapy (HRT) using oestrogen and progestin are at an increased risk of dying from lung cancer. However, HRT does not increase the incidence of lung cancer.

This comes out from a post-hoc analysis of 16,500 post-menopausal women who were part of a randomised, double-blind, placebo control trial to see the effect of HRT.

The Women’s Health Initiative (WHI) trial, which was undertaken in 40 centres in the U.S., was stopped abruptly in 2002 as the initial results showed that HRT had higher risk of cardiovascular disease, coronary heart disease, strokes, and breast cancer.

The analysis published online in The Lancet found that deaths from lung cancer could account for 43 per cent in the HRT group. Most of the deaths were from non-small-cell lung cancer — 62 deaths in the HRT group compared to 31 in the non-HRT group. HRT may also be delaying the diagnosis of lung lesions, thus increasing the risk of mortality.

The fact that mortality was higher suggests that combined HRT might be “stimulating the growth of already established non-small-cell lung cancer.” It found that smokers had a greater risk of dying from lung cancer when on HRT compared to their counterparts. Past smokers had an intermediate increase in risk.

It must be noted that the initial report of the trial showed no deaths from lung cancer during the period of treatment. The deaths occurred during the follow-up period.

While it has been shown that inhibiting new vessel formation is an effective intervention strategy in both breast and lung cancer, the present study shows strong evidence that oestrogen stimulates the formation of new blood vessels (angiogenesis).

There is a controversy whether oestrogen increases the risk of developing and dying from lung cancer. But most of these studies undertaken earlier had severe limitations thus making a meaningful interpretation difficult. The present study, unlike the earlier ones, does not suffer from those limitations and brings more clarity.

Unlike what has been shown by some studies, combined HRT does not “decrease the incidence of lung caner,” notes a Comment in the same issue of the journal. “These results seem to dispel the notion that progesterone is protective against lung cancer.”

One of the major limitations of the present study is that no information is available on the kind of treatment women got lung cancer after diagnosis.

However, the authors strongly advocate that the results from this study should be considered before initiation or continuation of HRT in postmenopausal women, especially those who are at a higher risk of developing lung cancer, such as smokers or who have a history of smoking.

There is also sufficient evidence to discontinue HRT once a woman is diagnosed with lung cancer.

“These results, along with the findings showing no protection against coronary heart disease, seriously question whether hormone replacement therapy has any role in medicine today,” the Comment notes. “It is difficult to presume that the benefits of routine use of such therapy for menopausal systems outweigh the increased risk of mortality, especially in the absence of improvement in the quality of life.”

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