Increased ovarian cancer risk associated with menopausal estrogen therapy is reduced by adding a progestin

Cancer. 2009 Feb 1;115(3):531-9. doi: 10.1002/cncr.23956.


Background: It has become increasingly clear that use of menopausal hormone therapy (HT) is associated with an increased risk of ovarian cancer; however, the effects by type of formulation and duration of use are less clear. A systematic review of the HT and ovarian cancer literature was conducted to identify population-based case-control studies, cohort studies, and randomized trials that examined effects by formulation of HT (estrogen-alone [ET] and estrogen plus progestin [EPT]) and duration of use.

Methods: Pub-Med ( was used to identify relevant publications through December 2007; 14 studies were identified. The authors abstracted relative risks (RRs) and 95% confidence intervals (CIs) in relation to duration of HT use (ET and EPT separately). The authors used the risk estimates per year of HT use if these were provided; otherwise, they calculated a duration-response for a log-linear model of the duration of HT use against risk.

Results: Ovarian cancer risk was increased among ET users (RR per 5 years of use, RR(5) = 1.22; 95% CI, 1.18-1.27; P < .0001), and a lower but still statistically significant increased risk was seen with EPT use (RR(5) = 1.10; 95% CI, 1.04-1.16; P = .001). The increased risk in ET users was statistically significantly higher than the increased risk in EPT users (P = .004).

Conclusions: ET use increases risk of ovarian cancer in a duration-dependent manner, and it appears that the addition of progestins blocks this effect, at least to some extent. Whether the effect of estrogens would be completely blocked if progestins were given every day is unclear.

Publication types

  • Meta-Analysis
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Estrogen Replacement Therapy / adverse effects*
  • Estrogens / administration & dosage
  • Female
  • Humans
  • Menopause*
  • Ovarian Neoplasms / epidemiology*
  • Progestins / administration & dosage*
  • Risk Assessment


  • Estrogens
  • Progestins