Hormone replacement therapy (HRT) using oestrogen and progestin increases the risk of death from lung cancer. This finding should be incorporated into risk-benefit discussions for women considering HRT, especially those at high risk of lung cancer. These are the conclusions of an article published in an upcoming edition of The Lancet, written by Professor Rowan Chlebowski, Los Angeles Biomedical Research Institute at Harbour-UCLA Medical Center, Torrance, CA, USA, and colleagues.

The authors looked at data from the Women's Health Initiative (WHI) trial. This large trial, of HRT (oestrogen plus progestin) in postmenopausal women, was stopped early when health risks were found to exceed benefits. At a mean follow-up of 5.6 years, participants assigned to HRT had higher risks of cardiovascular disease, coronary heart disease, stroke, venous thromboembolism, and breast cancer, and lower risks of fractures and colorectal cancers than did women assigned to placebo. All-cause mortality did not differ between study groups. Results from further follow-up (an additional 2.4 years, so 8 years in total) also suggested that the combined hormone therapy might increase mortality from lung cancer. To assess whether such an association exists, the authors looked at the number of lung cancers diagnosed in the trial over the entire follow-up period.

The WHI study was a randomised controlled trial done in 40 centres in the USA, involving 16,608 postmenopausal women aged 50-79 years with an intact uterus. They received either a once-daily tablet of 0.625 mg conjugated equine oestrogen plus 2.5 mg medroxyprogesterone acetate (8,506 women) or matching placebo (8,102). The researchers found that, after the 8 years total follow-up, more women died from lung cancer in the combined hormone therapy group than in the placebo group (73 vs 40 deaths; women in HRT group 71% more likely to die). This was mainly as a result of a higher number of deaths from non-small-cell lung cancer (NSCLC) in the combined therapy group (62 vs 31 deaths; women in HRT group 87% more likely to die specifically of NSCLC). Women in the HRT group were also 28% more likely to be diagnosed with lung cancer than those given placebo, although this finding was not statistically significant. Incidence and mortality rates of small-cell lung cancer were similar between groups.

The authors conclude: "Treatment with oestrogen plus progestin in postmenopausal women...increased the number of deaths from lung cancer, in particular deaths from non-small-cell lung cancer. These findings should be incorporated into risk-benefit discussions with women considering combined hormone therapy, especially those with a high risk of lung cancer...such as current smokers or long-term past smokers."

In an accompanying Comment, Dr Apar Kishor Ganti, University of Nebraska Medical Center, Omaha, NE, USA, says: "Because the optimum safe duration of hormone-replacement therapy in terms of lung-cancer survival is unclear, such therapy should probably be avoided in women at a high risk of developing lung cancer, especially those with a history of smoking. 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. It is difficult to presume that the benefits of routine use of such therapy for menopausal symptoms outweigh the increased risks of mortality, especially in the absence of improvement in the quality of life."