Estrogen Plus Progestin and Lung Cancer: Follow-up of the Women's Health Initiative Randomized Trial

Rowan T. Chlebowski, Heather Wakelee, Mary Pettinger, Thomas Rohan, Jingmin Liu, Michael Simon, Hilary Tindle, Catherine Messina, Karen Johnson, Ann Schwartz, Margery Gass, Jean Wactawski-Wende

Research output: Contribution to journalArticlepeer-review

31 Scopus citations


Introduction In the Women's Health Initiative (WHI) estrogen plus progestin trial, after 5.6 years' intervention and 8 years' median follow-up, more women died from lung cancer in the hormone therapy group (hazard ratio [HR], 1.71; 95% confidence interval [CI], 1.16-2.52; P =.01). Now after 14 years' median follow-up, we reexamined combined hormone therapy effects on lung cancer mortality. Patients and Methods In the WHI placebo-controlled trial, 16,608 postmenopausal women aged 50 to 79 years and with an intact uterus were randomly assigned to once-daily 0.625 mg conjugated equine estrogen plus 2.5 mg medroxyprogesterone acetate (n = 8506) or placebo (n = 8102). Incidence and mortality rates for lung cancer were assessed from multivariant proportional hazard models. Results After 14 years' cumulative follow-up, there were 219 lung cancers (0.19% per year) in the estrogen plus progestin group and 184 (0.17%) in the placebo group (HR, 1.12; 95% CI, 0.92-1.37; P =.24). While there were more deaths from lung cancer with combined hormone therapy (153 [0.13%] vs. 132 [0.12%], respectively), the difference was not statistically significant (HR, 1.09; 95% CI, 0.87-1.38; P =.45). The statistically significant increase in deaths from lung cancer observed during intervention in women assigned to estrogen plus progestin was attenuated after discontinuation of study pills (linear trend over time, P =.042). Conclusion The increased risk of death from lung cancer observed during estrogen plus progestin use was attenuated after discontinuation of combined hormone therapy.

Original languageEnglish (US)
Pages (from-to)10-17.e1
JournalClinical lung cancer
Issue number1
StatePublished - Jan 1 2016


  • Estrogen plus progestin
  • Lung cancer
  • Lung cancer mortality
  • Randomized trial
  • Women's Health Initiative

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine
  • Cancer Research


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