Researchers have shown that use of hormone therapy with estrogen plus progestin increases the risk of dying from
non-small cell lung cancer (NSCLC) in women with the disease. Lung cancer is the leading cause of cancer death
in U.S. women.
These findings are based on secondary analyses from the Women’s Health Initiative, a randomized, placebo-
controlled clinical trial evaluating the health effects of conjugated equine estrogen (CEE) plus
medroxyprogesterone acetate (MPA) in 16,608 mostly healthy postmenopausal women.
Previous research suggested that hormones play a role in non-small cell lung cancer because women tend to have
higher survival rates than men and respond better to certain therapies. However, this is the first study to examine a
specific correlation in a randomized clinical trial setting.
“Many women entering menopause have symptoms that make them consider hormone therapy,” said Rowan
Chlebowski, MD, PhD, a medical oncologist at the Los Angeles Biomedical Research Institute at Harbor-UCLA
Medical Center and the study’s lead author. “We already know that combined hormone therapy has more risks than
benefits, including a higher risk of stroke and breast cancer, the most common cancer in U.S. women. The link we
describe between hormone therapy with CEE plus MPA and death from non-small cell lung cancer should
influence discussions between physicians and women considering hormone therapy use, especially for those with a
This study looked at non-small cell lung cancer incidence and mortality during 5.6 years of intervention with
hormone therapy or placebo and 2.4 years of additional follow-up. While there was no significant difference in
NSCLC incidence between the two randomized groups, mortality after a NSCLC diagnosis was significantly higher
in the combined hormone therapy group: women in the hormone therapy group were 61 percent more likely to die
from non-small cell lung cancer than women in the placebo group (67 versus 39 deaths, respectively).
The researchers noted that the magnitude of the mortality risk of CEE plus MPA use in current smokers raises
particular concerns. The researchers report that one in 100 current smokers in the trial using combined hormone
therapy experienced an avoidable death from non-cell lung cancer during the eight years of this study. The
mortality rate was 3.4 percent among smokers in the hormone therapy group, versus 2.3 percent among smokers in
the placebo group over the 7.9 year study period.
Researchers noted that study strengths include the randomized, double-blind study design and the large, ethnically
diverse population; limitations include the secondary nature of the analyses as these findings were not a primary
objective of the trial. The researchers suspect their finding will prompt reconsideration of the risk-to-benefit
balance of combined hormone therapy use for menopause symptoms and prompt further studies, both preclinical
and clinical, on hormonal effects in NSCLC.