An article published Online First and in a future edition of The Lancet reports that hormone replacement therapy (HRT) using oestrogen and progestin increases the risk of death from lung cancer. This finding should be included into riskbenefit consideration for women considering HRT. It is especially essential for women at high risk of lung cancer. The article is the work of Professor Rowan Chlebowski, of the Los Angeles Biomedical Research Institute at HarbourUCLA Medical Center, Torrance, CA, USA, and colleagues.

Data from the Womens Health Initiative (WHI) trial was studied. This large trial, of HRT (oestrogen plus progestin) in postmenopausal women, was stopped prematurely when health risks were found to outweigh benefits. Followup after an average of 5.6 years showed that 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. Between study groups, allcause mortality did not fluctuate. In addition, results from further followup of an additional 2.4 years (totalling 8 years of monitoring) suggested that the combined hormone therapy might increase mortality from lung cancer. In order to corroborate this association, the authors evaluated the number of lung cancers diagnosed in the trial over the whole followup period.

The WHI study involved 16,608 postmenopausal women aged 50 to 79 years with an intact uterus. It was a randomised controlled trial that took place in 40 centres in the USA. A group of 8,506 women received a oncedaily tablet of 0.625 mg conjugated equine oestrogen plus 2.5 mg medroxyprogesterone acetate. The other group of 8,102 women received matching placebo. After the 8 years total followup the researchers found that more women died from lung cancer in the combined hormone therapy group than in the placebo group (73 compared to 40 deaths). In other words, women in the HRT group were 71 percent more likely to die. This was mostly as a result of a higher number of deaths from nonsmallcell lung cancer (NSCLC) in the combined therapy group (62 compared to 31 deaths). Women in the HRT group were 87 percent more likely to die particularly of NSCLC. In addition, women in the HRT group were 28 percent more likely to be diagnosed with lung cancer than those given placebo, although this finding was not statistically significant. Between groups, incidence and mortality rates of smallcell lung cancer were comparable.

Dr. Rowan T. Chlebowski, MD, PhD, Los Angeles Biomedical Research Institute (LA BioMed) chief of oncology and author of the study comments”Postmenopausal women, especially current smokers or longterm past smokers, should carefully consider these new lung cancer findings before initiating or continuing combined estrogen plus progestin use.”

The authors write in conclusion “Treatment with oestrogen plus progestin in postmenopausal women…increased the number of deaths from lung cancer, in particular deaths from nonsmallcell lung cancer. These findings should be incorporated into riskbenefit discussions with women considering combined hormone therapy, especially those with a high risk of lung cancer…such as current smokers or longterm past smokers.”

In a supplementary note, Dr Apar Kishor Ganti, University of Nebraska Medical Center, Omaha, NE, USA, remarks “Because the optimum safe duration of hormonereplacement therapy in terms of lungcancer 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 hormonereplacement 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.”

“Oestrogen plus progestin and lung cancer in postmenopausal women (Womens Health Initiative trial) a posthoc analysis of a randomised controlled trial”
Rowan T Chlebowski, Ann G Schwartz, Heather Wakelee, Garnet L Anderson, Marcia L Stefanick, JoAnn E Manson, Rebecca J Rodabough, Jason W Chien, Jean WactawskiWende, Margery Gass, Jane Morley Kotchen, Karen C Johnson, Mary Jo OSullivan, Judith K Ockene, Chu Chen, F Allan Hubbell, for the Womens Health Initiative Investigators
DOI 10.1016/S01406736(09)615269
The Lancet