Lung Cancer and Hormone Therapy: Bad News for Former and Current Smokers

Stephanie Portes-Antoine and Brandel France de Bravo, MPH, Cancer Prevention and Treatment Fund

Because of the risks of breast cancer, stroke, and other serious health problems, experts warn that women should only use hormone replacement therapy if the symptoms of menopause are causing major problems in their quality of life. In those situations, they should use the lowest possible dosage for the shortest period of time.[1] As a result of decreased use of hormone therapy, the breast cancer rate has declined in the United States in recent years. Nevertheless, the combined form of hormone therapy—consisting of estrogen and progestin—is still used by about 15% of postmenopausal women, with more than 25 million prescriptions written every year.[2]

As of June 2009, there is yet another reason to avoid taking hormone therapy. New research shows that hormone therapy can increase a woman’s chance of dying from lung cancer. Lung cancer is the leading cause of cancer deaths in women.

A large government study of post-menopausal women, called the Women’s Health Initiative (WHI), has been the major source of scientific information about the risks of hormone therapy since 2002. A new analysis published in June 2009 found that women who took hormone replacement therapy for five or more years were more likely to die of non-small cell lung cancer than women in the study who did not take hormone therapy.[3] Non-small cell lung cancer accounts for 85% of all lung cancer cases.

There were 16,000 women participating in the WHI study, ages 50 to 79, who either took Prempro, a drug combining estrogen and progestin, or took a placebo. Smoking rates were similar in both groups: half had never smoked, 40% were past smokers, and 10% were current smokers.

The risk of developing lung cancer was similar in both groups, but the women taking the hormones were about 60% more likely to die of lung cancer than the women taking a placebo. Not surprisingly, the risk was highest for current smokers, followed by past smokers, and lowest for never smokers. Among the women who smoked (former or current smokers), 3.4% of those taking hormone therapy died of lung cancer compared to 2.3% for women taking the placebo.

Among women who never smoked, 0.2% of hormone users died from lung cancer, compared with 0.1% of those who got the placebo. While the risk of dying from lung cancer was very small for women who never smoked, almost twice as many women died in the hormone group than in the placebo group. Because of the small number of non-smokers who died from lung cancer in this study, the increase is not statistically significant, which means it could have happened by chance. Research with larger samples is needed to tell us whether even non-smokers are at greater risk of lung cancer if they take hormone therapy.

These findings are consistent with previous research suggesting a link between hormone therapy and non-small cell lung cancer.[4,5] In the Journal of Clinical Oncology in 2006, Dr. Apar Kishor Ganti and his colleagues at the University of Nebraska reported that women with lung cancer who used hormone replacement therapy did not live as long as women who did not use hormones, even though the women receiving hormone therapy were younger.[6] Hormone therapy’s effect on survival was especially pronounced for women with a history of smoking.

According to Dr. Karen Reckamp, assistant professor of medicine at City of Hope Cancer Center in Duarte, California, “We see more and more non-smoking women getting lung cancer in general and often younger women. We know that there are estrogen receptors in the lung and in lung cancers and so there’s definitely an interaction between the development of lung cancer and hormones.”[7] The results from the Women’s Health Initiative study indicate that for most women, the risks of hormone therapy are much higher than the benefits, and we now know this is especially true for women who smoke or used to smoke.


  1. Santoro E., DeSoto M., and Lee JH. Hormone Therapy and Menopause. National Research Center for Women & Families. February 2009.
  2. Smith M. ASCO: Combined Hormone Therapy Linked to Lung Cancer Mortality. MedPage Today. May 31, 2009.
  3. Chlebowski RT et al. Non-small cell lung cancer and estrogen plus progestin use in postmenopausal women in the Women’s Health Initiative randomized clinical trial. Journal of Clinical Oncology, 2009 ASCO Annual Meeting Proceedings (Post-Meeting Edition). Vol 27, No 15S (May 20 Supplement), 2009: CRA1500.
  4. Negaard HFS, Eilertsen AL, Anders DA, Iversen PO. Decreased Lung Cancer Survival with Hormone Replacement Therapy: Caused by a Decreased Tissue Factor Pathway Inhibitor Level? Journal of Clinical Oncology. June 10, 2006; 24(7): 2683-2684.
  5. Siegfried JM. Hormone Replacement Therapy and Decreased Lung Cancer Survival. Journal of Clinical Oncology. January 1, 2006; 24(1): 9-10.
  6. Ganti AK, Sahmoun AE, Panwalkar AW, Tendulkar KK, Potti P. Hormone Replacement Therapy is Associated with Decreased Survival in Women in Lung Cancer. Journal of Clinical Oncology. January 1, 2006; 24(1):59-63.
  7. Karen Reckamp, M.D, assistant professor of medicine, thoracic oncology division, City of Hope Cancer Center, Duarte, Calif. May 30, 2009, American Society of Clinical