Unopposed estrogen and estrogen plus progestin menopausal hormone therapy and lung cancer risk in the NIH-AARP Diet and Health Study Cohort

Cancer Causes Control. 2012 Mar;23(3):487-96. doi: 10.1007/s10552-012-9904-2. Epub 2012 Feb 25.


Purpose: Previous studies have reported that lung cancer risk may be decreased, increased, or unaffected by prior use of menopausal hormone therapy (MHT).

Methods: To assess this issue further, we examined relationships among 118,008 women, ages 50-71 years who were recruited during 1995-1996 for the NIH-AARP Diet and Health Study and in whom 2,097 incident lung carcinomas were identified during follow-up through 2006. Multivariable Cox proportional hazards models estimated relative risks (RR) and 95% confidence intervals (CIs) associated with various measures of self-reported MHT use.

Results: We found no evidence that either estrogen therapy (ET)-only or estrogen plus progestin therapy (EPT) use was substantially related to subsequent lung cancer risk (respective RRs and 95% CIs for ever use = 0.97, 0.86-1.09 and 1.03, 0.90-1.17). There were no significant variations according to currency or duration of use of either formulation, nor was there evidence that risks varied within subgroups defined by cigarette smoking or body size. The absence of effect was seen for nearly all lung cancer subtypes, with the exception of an increased risk of undifferentiated/large cell cancers associated with long-term ET-only use (p (trend) = 0.02), a relationship not observed among EPT users.

Conclusions: Our results failed to support any substantial alterations in lung cancer risk associated with use of either unopposed estrogen or estrogen plus progestin MHT, even when detailed exposure measures and other risk predictors were considered.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Aged
  • Confidence Intervals
  • Estrogens / administration & dosage
  • Estrogens / adverse effects
  • Estrogens / therapeutic use*
  • Female
  • Hormone Replacement Therapy / adverse effects*
  • Hormone Replacement Therapy / methods
  • Humans
  • Lung Neoplasms / epidemiology*
  • Middle Aged
  • National Institutes of Health (U.S.)
  • Progestins / administration & dosage
  • Progestins / adverse effects
  • Progestins / therapeutic use*
  • Proportional Hazards Models
  • Risk
  • Risk Assessment / methods
  • Statistics as Topic
  • Surveys and Questionnaires
  • United States / epidemiology


  • Estrogens
  • Progestins